HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2 - PubMed (original) (raw)
Comparative Study
HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2
S P Lee et al. J Virol. 1993 Dec.
Abstract
Cytotoxic T-lymphocyte (CTL) responses induced by persistent Epstein-Barr virus (EBV) infection in normal B-lymphoid tissues could potentially be directed against EBV-positive malignancies if expression of the relevant viral target proteins is maintained in tumor cells. For malignancies such as nasopharyngeal carcinoma and Hodgkin's disease, this will require CTL targeting against the nuclear antigen EBNA1 or the latent membrane proteins LMP1 and LMP2. Here we analyze in detail a B95.8 EBV-reactivated CTL response which is specific for LMP2 and restricted through a common HLA allele, A2.1. We found that in vitro-reactivated CTL preparations from several A2.1-positive virus-immune donors contained detectable reactivity against A2.1-bearing target cells expressing either LMP2A or the smaller LMP2B protein from recombinant vaccinia virus vectors. Peptide sensitization experiments then mapped the A2.1-restricted response to a single epitope, the nonamer CLGGLLTMV (LMP2A residues 426 to 434), whose sequence accords well with the proposed peptide binding motif for A2.1. Most Caucasian and African virus isolates (whether of type 1 or type 2) were identical in sequence to B95.8 across this LMP2 epitope region, although 2 of 12 such isolates encoded a Leu-->Ile change at epitope position 6. In contrast, most Southeast Asian and New Guinean isolates (whether of type 1 or type 2) constituted a different virus group with a Cys-->Ser mutation at epitope position 1. CTLs raised against the B95.8-encoded epitope were nevertheless able to recognize these variant epitope sequences in the context of A2.1 whether they were provided exogenously as synthetic peptides or generated endogenously in B cells transformed with the variant viruses. A CTL response of this kind could have therapeutic potential in that it is directed against a protein expressed in many EBV-positive malignancies, is reactive across a range of virus isolates, and is restricted through a relatively common HLA allele.
Similar articles
- Conserved CTL epitopes within EBV latent membrane protein 2: a potential target for CTL-based tumor therapy.
Lee SP, Tierney RJ, Thomas WA, Brooks JM, Rickinson AB. Lee SP, et al. J Immunol. 1997 Apr 1;158(7):3325-34. J Immunol. 1997. PMID: 9120290 - Transporter (TAP)-independent processing of a multiple membrane-spanning protein, the Epstein-Barr virus latent membrane protein 2.
Lee SP, Thomas WA, Blake NW, Rickinson AB. Lee SP, et al. Eur J Immunol. 1996 Aug;26(8):1875-83. doi: 10.1002/eji.1830260831. Eur J Immunol. 1996. PMID: 8765034 - Developing immunotherapeutic strategies for the control of Epstein-Barr virus-associated malignancies.
Moss DJ, Khanna R, Sherritt M, Elliott SL, Burrows SR. Moss DJ, et al. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S80-3. J Acquir Immune Defic Syndr. 1999. PMID: 10430223 Review. - Co-Expression of the Epstein-Barr Virus-Encoded Latent Membrane Proteins and the Pathogenesis of Classic Hodgkin Lymphoma.
Vrzalikova K, Ibrahim M, Nagy E, Vockerodt M, Perry T, Wei W, Woodman C, Murray P. Vrzalikova K, et al. Cancers (Basel). 2018 Aug 24;10(9):285. doi: 10.3390/cancers10090285. Cancers (Basel). 2018. PMID: 30149502 Free PMC article. Review.
Cited by
- Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts.
Gary R, Aigner M, Moi S, Schaffer S, Gottmann A, Maas S, Zimmermann R, Zingsem J, Strobel J, Mackensen A, Mautner J, Moosmann A, Gerbitz A. Gary R, et al. J Transl Med. 2018 May 9;16(1):124. doi: 10.1186/s12967-018-1498-3. J Transl Med. 2018. PMID: 29743075 Free PMC article. - Peptide binding to MHC class I molecules: implications for antigenic peptide prediction.
Parker KC, Shields M, DiBrino M, Brooks A, Coligan JE. Parker KC, et al. Immunol Res. 1995;14(1):34-57. doi: 10.1007/BF02918496. Immunol Res. 1995. PMID: 7561340 Review. - Infection of human endothelial cells with Epstein-Barr virus.
Jones K, Rivera C, Sgadari C, Franklin J, Max EE, Bhatia K, Tosato G. Jones K, et al. J Exp Med. 1995 Nov 1;182(5):1213-21. doi: 10.1084/jem.182.5.1213. J Exp Med. 1995. PMID: 7595192 Free PMC article. - Expression of B7 (CD80) and CD40 antigens and the CD40 ligand in Hodgkin's disease is independent of latent Epstein-Barr virus infection.
Murray PG, Oates J, Reynolds GM, Crocker J, Young LS. Murray PG, et al. Clin Mol Pathol. 1995 Apr;48(2):M105-8. doi: 10.1136/mp.48.2.m105. Clin Mol Pathol. 1995. PMID: 16695980 Free PMC article. - CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections.
Cornberg M, Clute SC, Watkin LB, Saccoccio FM, Kim SK, Naumov YN, Brehm MA, Aslan N, Welsh RM, Selin LK. Cornberg M, et al. J Immunol. 2010 Mar 15;184(6):2825-38. doi: 10.4049/jimmunol.0902168. Epub 2010 Feb 17. J Immunol. 2010. PMID: 20164414 Free PMC article.
References
- Proc Natl Acad Sci U S A. 1973 Jan;70(1):190-4 - PubMed
- J Virol. 1992 May;66(5):3257-62 - PubMed
- Lancet. 1975 Jan 18;1(7899):142-3 - PubMed
- Clin Chem. 1975 Jul;21(8):1159-66 - PubMed
- Eur J Immunol. 1982 Dec;12(12):1012-8 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials