Corecognition of HLA-A1 and HLA-DPw3 by a human CD4 super(+) alloreactive T lymphocyte clone

We have generated an alloreactive proliferative T cell clone that only is stimulated by HLA-DPw3 super(+) antigen presenting cells (APC) that at the same time carry HLA-A1. The T cell clone is CD4 super(+), and the proliferation is blocked by anti-DP monoclonal antibodies and not by antibodies towards other class II or towards class I molecules. Family studies show that APC with A1 and DPw3 on different haplotypes (trans) are able to stimulate the clone, and an HLA recombinant family gives evidence that the class I-carrying part of the haplotype is necessary for stimulation to occur. Stimulation is also observed with mixtures of APC expressing DPw3 and APC expressing A1, and likewise, DPw3 super(+) APC become stimulatory when preincubated with supernatants from A1-positive cells. Our studies suggest that major histocompatibility complex (MHC) class I peptides presented by class II are allostimulatory and that APC can process MHC molecules that presumably are presented as allele-specific peptides in the context of other MHC molecules. (DBO)