Distinct recognition by two subsets of T cells of an MHC class II-peptide complex.
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-A(k) 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-A(k) molecules. We discuss the mode of generation of the various T cells and their biological relevance.
Pu
Zheng
Z
Department of Pathology and Immunology, and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Carrero
Javier A
JA
Unanue
Emil R
ER
D000595:Amino Acid Sequence; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II