Dolores Jaraquemada - Profile on Academia.edu (original) (raw)

Papers by Dolores Jaraquemada

Double negative NKT cells may be involved in the Th1 or Th2 predominance in autoimmune T cell infiltrates

HLA-DR-DQ Associations in British Caucasoids and Nigerian Negroids

HLA-Dw Heterogeneity and its Relationship with HLA - DR antigens in Nigerians

HLA-DP Antigens in Nigerians

Alpha and Beta Chain Polymorphisms of HLA-DR4

Segregation Analysis of PLT Reagents in Families

From the data included in the central analysis of DP, 36 families could be used for segregation a... more From the data included in the central analysis of DP, 36 families could be used for segregation analysis. The numbers of families informative for each DP allele are listed in Table 1. Only two families were informative for DPwl, since primed lymphocyte (PL) reagent 20 did not function well in several of the larger experiments. For the DPw2 specificity, nine informative families were analyzed. In one family, one child carried the DPw2 specificity who did not have the expected HLA haplotype carrying this specificity in the parent and three other children. Since data on GLO was not available, a recombination event could not be confirmed. For the specificities DPw2-DPw4, one child in each of several families was found to lack an antigen, although inheriting the given HLA haplotype with which the DP specificity was associated in at least two other children.

Functional heterogeneity of HLA-class II determinants: the role of HLA-DQ as a modulator of cell-mediated responses

PubMed, Feb 1, 1987

DNA Restriction Fragment Length Polymorphism of the Human Class II Genes as Analyzed by Southern Blotting Technique

Springer eBooks, 1984

The human HLA-D region class II antigens each consist of two non-covalently linked trans-membrane... more The human HLA-D region class II antigens each consist of two non-covalently linked trans-membrane glycoprotein subunits: an α heavy chain of 32–35 kd and a β light chain of 28–30 kd [1]. They are encoded by a complex multigene family consisting of several loci within the major histocompatibility complex on chromosome 6 [1]. Their products, which are primarily represented on B cells, monocytes and activated T cells, participate in several cellular immune functions. These include antigen presentation and cell—cell recognition. They are also associated with susceptibility/resistance to some diseases [1]. There are at least three distinct class II allelic series - HLA-DR, BR and DQ - all detectable by molecular and serological assays [2]. A fourth serologically defined class II system has been called “SB” (now DP) because it is thought by some to correspond to the antigens defined by primed lymphocyte typing [5]. In addition, there are the HLA-D specificities which are defined by mixed lymphocyte culture testing. Most of these specificities correlate closely with HLA-DR in Caucasoids but not in Negroids and Mongoloids [3]. The precise relationship between these “MLC determinants” and the molecules described above has not yet been established.

Collaborative scheme for tissue typing and matching in renal transplantation. X. Effect of HLA-A, B, D, and DR matching and pretransplant blood transfusion on 769 cadaver renal grafts

PubMed, Mar 1, 1979

ABSTRACT

HLA-D and DR determinants in rheumatoid arthritis

PubMed, Jun 1, 1979

HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals

Journal of Immunology, Nov 1, 1990

The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using mu... more The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRalpha and either DR2a or DR2b beta-chain cDNA. DR2a and DR2b represent the two isotypic DRbeta chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but rather to the binding of different MBP peptides to DR2a molecules.

Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis

Annals of the Rheumatic Diseases, Apr 22, 2022

ObjectiveRheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly ... more ObjectiveRheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA.MethodsHLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry.ResultsWe identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity.ConclusionsWe significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.

Journal of Experimental Medicine, Mar 1, 1990

The class II antigens ofthe human MHC are cell surface heterodimers composed of noncovalently lin... more The class II antigens ofthe human MHC are cell surface heterodimers composed of noncovalently linked 35-kD a chains and 29-kD (3 chains. These antigens are present on macrophages, B lymphocytes, and other APC (for review, see reference 1). Class II antigens are capable of binding immunogenic peptides and thereby serve as ligand for the TCR (2, 3). Recent experiments have demonstrated that class II proteins are also functional ligands for the T cell surface antigen CD4 (4-6). Class 11 antigens display a very high degree ofallelic polymorphism, presumably to enable the species to mount the widest possible range of immune responses. At the individual level, diversity in class II antigens is provided by the existence ofthree isotypic forms in man, named HLA-DR, HLA-DQ, and HLA-DP. These isotypes are characterized by nonpolymorphic sequences unique to each isotypic a and a chain. HLA-DR, the immunodominant class II isotype, has a nonpolymorphic a chain and a highly polymorphic achain. Most of the allelic variation in DR a chains

Journal of Experimental Medicine, Feb 1, 1987

CTL recognize foreign antigens on the surface of target cells in association with MHC molecules. ... more CTL recognize foreign antigens on the surface of target cells in association with MHC molecules. Alloreactive cells, which recognize MHC alloantigens as targets, exist as a significant fraction of the T cell repertoire in mature individuals and can be activated in vitro as a result of the allogeneic mixed lymphocyte reaction. MHC antigen variants distinguishable by CTL have been used to establish that changes in various positions of their amino acid sequence result in simultaneous alteration of epitopes recognized by both alloreactive and MHCrestricted CTL (1-5). In addition, some CTL show crossreactivity between class I allodeterminants and self-class I-restricted foreign determinants (6, 7). Thus, closely related epitopes on the MHC molecule could be involved in both allorecognition and MHC restriction. The existence of these crossreactions is in contrast with the virtual absence of CTL showing crossreactivity between class I and class II antigens. This lack of crossreactivity also holds at antibody level and is a well-known fact in HLA serology. With a few exceptions, human CTL that recognize class I antigens express the CD8(T8) molecule on their surface, whereas those recognizing class 11 antigens express CD4(T4) (8). Anti-CD8 and anti-CD4 antibodies can prevent conjugate formation between target cells and their specific CTL (9-11). These observations prompted the assumption that CD8 and CD4 are involved in the recognition of nonpolymorphic sites on the class I and class 11 molecules, respectively (12). However, direct evidence for the interaction of CD8 or CD4 with MHC antigens has not been provided. A non-MHC-dependent regulatory role in T cell triggering has also been suggested for CD4 and CD8 (13, 14). The present work shows the characterization of three alloreactive CD8' CTL clones that display simultaneous lytic ability for both HLA-B27 .1 + cells and HLA-DR2+ targets expressing certain DR2-associated Dw determinants. For each of these clones, an anti-CD8 mAb inhibited class I-, but not class II-directed killing, whereas lysis of all target cells was inhibited by an anti-CD3 antibody .

Response to: Correspondence on “HLA-DR ‘naturally’ presented peptides: you will find what you have pulsed with” by Maggi et al

Annals of the Rheumatic Diseases, May 20, 2022

The Functional Heterogeneity of HLA Class II Determinants

The original discovery by Navarrete et al. (1) that HLA-DQ and HLA-DR specificities are different... more The original discovery by Navarrete et al. (1) that HLA-DQ and HLA-DR specificities are differentially expressed on leukemic cells and particularly that HLA-DQ is absent from acute myeloid leukemic cells, led us to investigate whether HLA-DQ has a specific unique role in the immune response. If so, the absence of HLA-DQ on the tumor cells may be advantageous for the development of leukemia. This concept was supported by the experiments of Corte et al. (2), which showed that HLA-DQ antibody was able to prevent the in vitro generation of cytotoxic T cells. These findings were subsequently confirmed in our laboratory (3). Previous genetic experiments in the mouse in which recombinant congenic mouse strains were employed also suggested that H-2 E (the functional counterpart of HLA-DQ) is important in the generation of cytotoxic T cells.

Changing Antigenic Profiles of HLA Class II Antigens on Activated T Cells and Their Biological Effects

Springer eBooks, 1986

When the immune system is activated, complex cell-cell interactions are initiated which ultimatel... more When the immune system is activated, complex cell-cell interactions are initiated which ultimately lead to one or more of several well-known kinds of response. The quality and extent of these responses depend largely upon the particular subset of immune cells which are activated and the balance between the various subsets of activated and other cells involved. The cells which participate in the immune response interact through MHC and other cell membrane molecules. An important consequence of activation is the appearance of molecules on the cell surface which are not normally detectable on resting cells. T cells, for example, when activated, undergo profound changes such as increases in RNA, DNA and rate of protein synthesis, accompanied by the appearance of large nucleoli and abundant euchromatin and a vast increase in the amount of endoplasmic reticulum. These processes culminate in phenotypic variations, including changes in the MHC antigenic profile.

Journal of Immunology, Aug 1, 1987

Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid chang... more Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid changes within a single polypeptide segment generate polymorphism in HLA-B27.

Journal of Immunology, Aug 15, 1994

Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of... more Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of the MHC.

First Level Testing of HLA-DR4-Associated New HLA-D Specificities: Dw13 (DB3), Dw14 (LD40), Dw15 (DYT), and DKT2

Springer eBooks, 1984

HLA-DR4 is associated with several mixed lymphocyte culture (MLC)-defined HLA-D specificities. In... more HLA-DR4 is associated with several mixed lymphocyte culture (MLC)-defined HLA-D specificities. In addition to Dw4 and Dw10, four tentative Dw specificities were previously described: Dw13 [1, 2], Dw14 [3], Dw15 [4] and DKT2 [5].

Double negative NKT cells may be involved in the Th1 or Th2 predominance in autoimmune T cell infiltrates

HLA-DR-DQ Associations in British Caucasoids and Nigerian Negroids

HLA-Dw Heterogeneity and its Relationship with HLA - DR antigens in Nigerians

HLA-DP Antigens in Nigerians

Alpha and Beta Chain Polymorphisms of HLA-DR4

Segregation Analysis of PLT Reagents in Families

From the data included in the central analysis of DP, 36 families could be used for segregation a... more From the data included in the central analysis of DP, 36 families could be used for segregation analysis. The numbers of families informative for each DP allele are listed in Table 1. Only two families were informative for DPwl, since primed lymphocyte (PL) reagent 20 did not function well in several of the larger experiments. For the DPw2 specificity, nine informative families were analyzed. In one family, one child carried the DPw2 specificity who did not have the expected HLA haplotype carrying this specificity in the parent and three other children. Since data on GLO was not available, a recombination event could not be confirmed. For the specificities DPw2-DPw4, one child in each of several families was found to lack an antigen, although inheriting the given HLA haplotype with which the DP specificity was associated in at least two other children.

Functional heterogeneity of HLA-class II determinants: the role of HLA-DQ as a modulator of cell-mediated responses

PubMed, Feb 1, 1987

DNA Restriction Fragment Length Polymorphism of the Human Class II Genes as Analyzed by Southern Blotting Technique

Springer eBooks, 1984

The human HLA-D region class II antigens each consist of two non-covalently linked trans-membrane... more The human HLA-D region class II antigens each consist of two non-covalently linked trans-membrane glycoprotein subunits: an α heavy chain of 32–35 kd and a β light chain of 28–30 kd [1]. They are encoded by a complex multigene family consisting of several loci within the major histocompatibility complex on chromosome 6 [1]. Their products, which are primarily represented on B cells, monocytes and activated T cells, participate in several cellular immune functions. These include antigen presentation and cell—cell recognition. They are also associated with susceptibility/resistance to some diseases [1]. There are at least three distinct class II allelic series - HLA-DR, BR and DQ - all detectable by molecular and serological assays [2]. A fourth serologically defined class II system has been called “SB” (now DP) because it is thought by some to correspond to the antigens defined by primed lymphocyte typing [5]. In addition, there are the HLA-D specificities which are defined by mixed lymphocyte culture testing. Most of these specificities correlate closely with HLA-DR in Caucasoids but not in Negroids and Mongoloids [3]. The precise relationship between these “MLC determinants” and the molecules described above has not yet been established.

Collaborative scheme for tissue typing and matching in renal transplantation. X. Effect of HLA-A, B, D, and DR matching and pretransplant blood transfusion on 769 cadaver renal grafts

PubMed, Mar 1, 1979

ABSTRACT

HLA-D and DR determinants in rheumatoid arthritis

PubMed, Jun 1, 1979

HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals

Journal of Immunology, Nov 1, 1990

The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using mu... more The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRalpha and either DR2a or DR2b beta-chain cDNA. DR2a and DR2b represent the two isotypic DRbeta chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but rather to the binding of different MBP peptides to DR2a molecules.

Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis

Annals of the Rheumatic Diseases, Apr 22, 2022

ObjectiveRheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly ... more ObjectiveRheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA.MethodsHLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry.ResultsWe identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity.ConclusionsWe significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.

Journal of Experimental Medicine, Mar 1, 1990

The class II antigens ofthe human MHC are cell surface heterodimers composed of noncovalently lin... more The class II antigens ofthe human MHC are cell surface heterodimers composed of noncovalently linked 35-kD a chains and 29-kD (3 chains. These antigens are present on macrophages, B lymphocytes, and other APC (for review, see reference 1). Class II antigens are capable of binding immunogenic peptides and thereby serve as ligand for the TCR (2, 3). Recent experiments have demonstrated that class II proteins are also functional ligands for the T cell surface antigen CD4 (4-6). Class 11 antigens display a very high degree ofallelic polymorphism, presumably to enable the species to mount the widest possible range of immune responses. At the individual level, diversity in class II antigens is provided by the existence ofthree isotypic forms in man, named HLA-DR, HLA-DQ, and HLA-DP. These isotypes are characterized by nonpolymorphic sequences unique to each isotypic a and a chain. HLA-DR, the immunodominant class II isotype, has a nonpolymorphic a chain and a highly polymorphic achain. Most of the allelic variation in DR a chains

Journal of Experimental Medicine, Feb 1, 1987

CTL recognize foreign antigens on the surface of target cells in association with MHC molecules. ... more CTL recognize foreign antigens on the surface of target cells in association with MHC molecules. Alloreactive cells, which recognize MHC alloantigens as targets, exist as a significant fraction of the T cell repertoire in mature individuals and can be activated in vitro as a result of the allogeneic mixed lymphocyte reaction. MHC antigen variants distinguishable by CTL have been used to establish that changes in various positions of their amino acid sequence result in simultaneous alteration of epitopes recognized by both alloreactive and MHCrestricted CTL (1-5). In addition, some CTL show crossreactivity between class I allodeterminants and self-class I-restricted foreign determinants (6, 7). Thus, closely related epitopes on the MHC molecule could be involved in both allorecognition and MHC restriction. The existence of these crossreactions is in contrast with the virtual absence of CTL showing crossreactivity between class I and class II antigens. This lack of crossreactivity also holds at antibody level and is a well-known fact in HLA serology. With a few exceptions, human CTL that recognize class I antigens express the CD8(T8) molecule on their surface, whereas those recognizing class 11 antigens express CD4(T4) (8). Anti-CD8 and anti-CD4 antibodies can prevent conjugate formation between target cells and their specific CTL (9-11). These observations prompted the assumption that CD8 and CD4 are involved in the recognition of nonpolymorphic sites on the class I and class 11 molecules, respectively (12). However, direct evidence for the interaction of CD8 or CD4 with MHC antigens has not been provided. A non-MHC-dependent regulatory role in T cell triggering has also been suggested for CD4 and CD8 (13, 14). The present work shows the characterization of three alloreactive CD8' CTL clones that display simultaneous lytic ability for both HLA-B27 .1 + cells and HLA-DR2+ targets expressing certain DR2-associated Dw determinants. For each of these clones, an anti-CD8 mAb inhibited class I-, but not class II-directed killing, whereas lysis of all target cells was inhibited by an anti-CD3 antibody .

Response to: Correspondence on “HLA-DR ‘naturally’ presented peptides: you will find what you have pulsed with” by Maggi et al

Annals of the Rheumatic Diseases, May 20, 2022

The Functional Heterogeneity of HLA Class II Determinants

The original discovery by Navarrete et al. (1) that HLA-DQ and HLA-DR specificities are different... more The original discovery by Navarrete et al. (1) that HLA-DQ and HLA-DR specificities are differentially expressed on leukemic cells and particularly that HLA-DQ is absent from acute myeloid leukemic cells, led us to investigate whether HLA-DQ has a specific unique role in the immune response. If so, the absence of HLA-DQ on the tumor cells may be advantageous for the development of leukemia. This concept was supported by the experiments of Corte et al. (2), which showed that HLA-DQ antibody was able to prevent the in vitro generation of cytotoxic T cells. These findings were subsequently confirmed in our laboratory (3). Previous genetic experiments in the mouse in which recombinant congenic mouse strains were employed also suggested that H-2 E (the functional counterpart of HLA-DQ) is important in the generation of cytotoxic T cells.

Changing Antigenic Profiles of HLA Class II Antigens on Activated T Cells and Their Biological Effects

Springer eBooks, 1986

When the immune system is activated, complex cell-cell interactions are initiated which ultimatel... more When the immune system is activated, complex cell-cell interactions are initiated which ultimately lead to one or more of several well-known kinds of response. The quality and extent of these responses depend largely upon the particular subset of immune cells which are activated and the balance between the various subsets of activated and other cells involved. The cells which participate in the immune response interact through MHC and other cell membrane molecules. An important consequence of activation is the appearance of molecules on the cell surface which are not normally detectable on resting cells. T cells, for example, when activated, undergo profound changes such as increases in RNA, DNA and rate of protein synthesis, accompanied by the appearance of large nucleoli and abundant euchromatin and a vast increase in the amount of endoplasmic reticulum. These processes culminate in phenotypic variations, including changes in the MHC antigenic profile.

Journal of Immunology, Aug 1, 1987

Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid chang... more Structural analysis of an HLA-B27 population variant, B27f. Multiple patterns of amino acid changes within a single polypeptide segment generate polymorphism in HLA-B27.

Journal of Immunology, Aug 15, 1994

Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of... more Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of the MHC.

First Level Testing of HLA-DR4-Associated New HLA-D Specificities: Dw13 (DB3), Dw14 (LD40), Dw15 (DYT), and DKT2

Springer eBooks, 1984

HLA-DR4 is associated with several mixed lymphocyte culture (MLC)-defined HLA-D specificities. In... more HLA-DR4 is associated with several mixed lymphocyte culture (MLC)-defined HLA-D specificities. In addition to Dw4 and Dw10, four tentative Dw specificities were previously described: Dw13 [1, 2], Dw14 [3], Dw15 [4] and DKT2 [5].

Composition of the HLA-DR-associated human thymus peptidome