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

Paul M. Allen, Gary R. Matsueda, Robert J. Evans, James B. Dunbar, Garland R. Marshall, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

257 Scopus citations

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 molecule1. 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 mice2,3. This peptide binds with a Kd of ~3 μM to I-Ak molecules1. We have already ascertained that (1) the 10-mer HEL(52-61) is the shortest stimulatory peptide4; (2) the Leu56 residue, the only residue different from mouse lysozyme, is responsible for the immunogenicity4; (3) the Leu56 and Tyr53 residues are critical for recognition by the T-cell receptor5 and (4) HEL(46-61) generates multiple determinants when it associated with the I-Ak molecule4,6. 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 receptor7,8. The two sites do not appear to be laterally separable in this peptide5 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 α-helical conformation as it is bound to I-Ak and recognized by the T-cell receptor.

Original languageEnglish
Pages (from-to)713-715
Number of pages3
JournalNature
Volume327
Issue number6124
DOIs
StatePublished - Jan 1 1987

Fingerprint Dive into the research topics of 'Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope'. Together they form a unique fingerprint.

Cite this