A CYTOTOXIC T-LYMPHOCYTE CLONE CAN RECOGNIZE THE SAME NATURALLY-OCCURRING SELF-PEPTIDE IN ASSOCIATION WITH A SELF AND A NONSELF CLASS-I MHC PROTEIN

The alloreactive CD8(+) cytotoxic T lymphocyte (CTL) clone 2C was previously shown to recognize complexes made up of the class I MHC (MHC-I) molecule L(d) and an octapeptide (LSPFPFDL, termed p2Ca) isolated from tissues of H-2(d) mice. Because peptide p2Ca has also been found in BALB.B (H-2(b)) mice, the strain from which clone 2C originated, the question arises as to whether these T cells can recognize peptide p2Ca in association with a self MHC protein of the H-2(b) haplotype. Here we show that 2C CTL do indeed recognize peptide p2Ca in association with K-b On the surface of H-2(b) cells or on transfected cells expressing K-b, but that an approximately 1000-fold higher concentration of this peptide is required to sensitize K-b+ than L(d+) target cells for lysis by 2C cells. However, the peptide's binding to Kb was not much weaker than to L(d), With only an approximately 10-fold difference in the respective equilibrium constants. These results predict that the T cell receptor (TcR) of clone 2C has a much lower intrinsic affinity for p2Ca-K-b complexes than for p2Ca-L(d) complexes, and they provide some quantitative limits on the requirements for triggering T cell-mediated autoimmune reactivity.