title: CD8 expression alters the fine specificity of an alloreactive MHC class I-specific T hybridoma.
abstract: The influence of CD8 on the fine specificity of MHC class I-restricted T cell allorecognition was evaluated by comparing the reactivity of CD8- and CD8-transfected forms of an allospecific, H-2Kb-restricted T hybridoma. The CD8- T hybridoma responded to cells expressing H-2Kb, H-2Kbm6, and the individual H-2Kb----bm10 back 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-2Kbm10, H-2Kbm8, the individual H-2Kb----bm10 back mutants 163T----A and 167W----S, and the individual H-2Kb----bm8 back 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-2Kb and H-2Kbm6 molecules, as well as APC expressing H-2Kbm10 (weakly), H-2Kbm8, and all five individual H-2Kb----bm10 and the two H-2Kb----bm8 back mutants 22Y----F and 24E----S. The mutations which distinguish the T cell recognition of both H-2Kbm10 and H-2Kbm8 from H-2Kb are predicted to control the interaction of these class I molecules with antigenic peptides in the binding site, implying an important role for peptide antigen in T cell allorecognition. Nonetheless, CD8 expression by the H-2Kb-restricted T cells conferred novel or enhanced alloreactivity with cells expressing H-2Kbm10, H-2Kbm8, and each of the individual H-2Kb----bm10 and H-2Kb----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 ligand recognized by these alloreactive T cells.
authors.affiliation: Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Blok
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
authors.forename: L
authors.initials: L
authors.lastname: Pease
authors.forename: R K
authors.initials: RK
authors.lastname: Ribaudo
authors.forename: J
authors.initials: J
authors.lastname: Schneck
authors.forename: J
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens; D004247:DNA / Q000235:genetics; D006183:H-2 Antigens / Q000235:genetics; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D004247:DNA