Distinct recognition by two subsets of T cells of an MHC class II-peptide complex

Zheng Pu, Javier A. Carrero, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


We examine here the nature of the differential recognition by CD4+ T cells of a single peptide from hen-egg white lysozyme (HEL) presented by I-Ak class II MHC molecules. Two subsets of T cells (called A and B) interact with the same peptide, each in unique ways that reflect the nature of the complex of peptide and MHC. We show that the A and B set of T cells can be distinguished by their functional interaction with the three T cell receptor (TCR) contact residues of the bound peptide. The dominant peptide of HEL selected from processing is bound in a single register where a critical TCR contact residue is situated about the middle of the core segment of the peptide: all T cells establish functional contact with it. Three sets of T cells, however, can be distinguished by their differential recognition of two TCR contacts situated at the amino and carboxyl sides of the central TCR contact residue. Type A T cells, the conventional cells that see the peptide after processing of HEL, need to recognize all three TCR contact residues. In contrast, the type B T cells recognize the peptide given exogenously, but not when processed: these T cells recognize either one of the peripheral TCR contact residues, indicating a much more flexible interaction of peptide with I-Ak molecules. We discuss the mode of generation of the various T cells and their biological relevance.

Original languageEnglish
Pages (from-to)8844-8849
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jun 25 2002


  • Antigen presentation
  • Antigen-presenting cells
  • Histocompatibility molecules
  • T cell receptors


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