Peptide-dependent recognition of H–2K^b by alloreactive cytotoxic T lymphocytes

Abstract

ANTIGEN-specific T lymphocytes appear to recognize foreign antigens in the form of peptide fragments presented within the antigen-binding groove of class I or class II molecules encoded by the major histocompatibility complex (MHC). Alloreactive T cells also show specificity for MHC molecules, and various reports suggest that residues of the MHC molecules constitute at least part of the ligand to which alloreactive T-cell receptors bind^1–4. The X-ray crystal structure of the human MHC class I molecule, HLA-A2⁵, has provided evidence to strengthen the argument that MHC-bound self-peptide⁶ might also contribute to such recognition⁷. We now provide direct evidence for this, showing that at least some alloreactive cytotoxic T lymphocyte clones recognize peptide fragments derived from cytoplasmic proteins. We reasoned that if self-peptides were involved in allorecognition, then the sequence of some of these peptides could vary between species, resulting in species-restricted distribution of the relevant ligand (s)^8–11. Several alloreactive cytotoxic T lymphocyte clones specific for H–2K^b, expressed by the murine cell line EL4, did not lyse a human-cell transfectant expressing the H–2K^b molecule (Jurkat-K^b cells). However, these clones were able to lyse Jurkat-K^b cells sensitized by preincubation with an EL4 cytoplasmic extract cleaved by cyanogen bromide. The sensitizing activity from this extract was destroyed by protease and appeared to be due to a peptide consisting of 10 to 15 amino acids.