MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition

Antigen-specific T cell recognition is dependent on the functional density of the TCR-ligand, which consists of specific MHC molecules and a specifica lly bound peptide. We have examined the influence of the affinity and conce ntration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4+, DQA1*0501/DQB1*0201 (DQ2.1)-restricted, HSV-2- specific T cell clone. Using antigen peptide analogs with different mutatio ns of known DQ2-anchor residues, T cell response was reduced in an peptide- affinity and - concentration specific manner. The decrease using weaker bin ding peptides was gradual as stimulation with a peptide with intermediate a ffinity yielded intermediate T cell proliferation and the poorest binding p eptide induced an even weaker T cell response. MHC class II density on the APC was modified using DQ2 homo- and heterozygous B-LCLs as APCs, however t his variation of MHC concentration had no effect on T cell proliferation. W e interpret this as a reflection of a low threshold for activation of the T cell clone, in which peptide-MHC avidity is the over-riding determinant of the strength of ligand signal. Human Immunology 60, 608-618 (1999). (C) Am erican Society for Histocompatibility and Immunogenetics, 1999 Published by Elsevier Science Inc.