CD8 expression alters the fine specificity of an alloreactive MHC class l-specific T hybridoma

The influence of CD8 on the fine specificity of MHC class l-restrlcted T cell allorecognition was evaluated by comparing the reactivity of CD8^- and CD8-transfected forms of an allospecific, H-2K^b-restricted T hybridoma. The CD8^- T hybridoma responded to cells expressing H-2K^b, H-2K^bm6and the individual H-2K^b-bm10back mutations 165V-M, 173K-E, and 174N-L. Under the same conditions the CD8- T hybridoma responded poorly or not at all to cells expressing H-2k^bm10, H-2K^bm8, the individual H-2K^bm1010 back mutants 163T-A and 167W-S, and the Individual H-2K^b-bm8back mutations 22Y-F and 24E-S. In contrast, T hybridoma cells expressing high levels of CD8 reacted strongly with antigen presenting cells (APC) expressing H-2K^b and H-2K^bm66 molecules, as well as APC expressing H-2K^bm10 (weakly), H-2Kb-^bm8 and all five individual H-2Kb-^bm10 and the two H-2K^b-bm8 back mutants 22Y↑F and 24E↑S. The mutations which distinguish the T cell recognition of both H-2K^bm10 and H=-2K^bm8 from H-2K^b are predicted to control the interaction of these class I molecules with antlgenic peptides In the binding site, Implying an important role for peptide antigen In T cell allorecognition. Nonetheless, CD8 expression by the H-2K^b-restricted T cells conferred novel or enhanced alloreactivlty with cells expressing H-2K^bm10, H-2K^bm8, and each of the individual H-2K^bm10 and H-2K^b-bm8 back mutants. These findings reflect an Important role for CD8 in influencing the fine specificity of MHC class I recognition by T cells and may Indicate a limited structural role for peptide antigen in defining the llgand recognized by these alloreactive T cells