Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope - PubMed (original) (raw)

PMID: 2439915
DOI: 10.1038/327713a0

Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope

P M Allen et al. Nature. 1987.

Abstract

The precise molecular structure of the antigenic determinant recognized by the T-cell receptor of the CD4-positive cell has not been completely resolved. A major advance in our understanding of this issue has been made by our demonstration of a direct association between an immunogenic peptide and a purified Ia molecule. The most likely and economical hypothesis is that antigen binds directly to an Ia molecule creating the antigenic determinant and that this antigen-Ia complex is recognized by the T-cell receptor. We examined in detail a determinant of hen egg-white lysozyme (HEL) contained in the tryptic fragment HEL(46-61), recognized by T cells in H-2k strains of mice. This peptide binds with a Kd of approximately 3 microM to I-Ak molecules. We have already ascertained that (1) the 10-mer HEL(52-61) is the shortest stimulatory peptide; (2) the Leu56 residue, the only residue different from mouse lysozyme, is responsible for the immunogenicity; (3) the Leu56 and Tyr53 residues are critical for recognition by the T-cell receptor and (4) HEL(46-61) generates multiple determinants when it associated with the I-Ak molecule. If antigen and Ia interact, the antigen must have two features: it must bind to an Ia molecule and also interact with the T-cell receptor. The two sites do not appear to be laterally separable in this peptide and are therefore probably composed of distinct but interspersed amino-acid residues. We have now identified the three residues of HEL(52-61) that contact the T-cell receptor and three other residues that contact the I-Ak molecule. From modelling studies we also propose that HEL(52-61) assumes an alpha-helical conformation as it is bound to I-Ak and recognized by the T-cell receptor.

PubMed Disclaimer

Cited by

Distinct recognition by two subsets of T cells of an MHC class II-peptide complex.
Pu Z, Carrero JA, Unanue ER. Pu Z, et al. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8844-9. doi: 10.1073/pnas.092260499. Proc Natl Acad Sci U S A. 2002. PMID: 12084929 Free PMC article.
Role of interaction of CD2 molecules with lymphocyte function-associated antigen 3 in T-cell recognition of nominal antigen.
Koyasu S, Lawton T, Novick D, Recny MA, Siliciano RF, Wallner BP, Reinherz EL. Koyasu S, et al. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2603-7. doi: 10.1073/pnas.87.7.2603. Proc Natl Acad Sci U S A. 1990. PMID: 1690889 Free PMC article.
Two genetically identical antigen-presenting cell clones display heterogeneity in antigen processing.
Michalek MT, Benacerraf B, Rock KL. Michalek MT, et al. Proc Natl Acad Sci U S A. 1989 May;86(9):3316-20. doi: 10.1073/pnas.86.9.3316. Proc Natl Acad Sci U S A. 1989. PMID: 2470101 Free PMC article.
Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules.
Harding CV, Roof RW, Allen PM, Unanue ER. Harding CV, et al. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2740-4. doi: 10.1073/pnas.88.7.2740. Proc Natl Acad Sci U S A. 1991. PMID: 2011583 Free PMC article.

Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope - PubMed (original) (raw)