Alteration of the T cell self-specificity repertoire by treatment with anti-Ia antibody during embryonic life.

The effect of anti-Ia antibody on the development of murine neonatal self-Ia-reactive T lymphocytes in the thymus was studied. A C57BL/6 (B6) mouse pregnant with (B6 X C3H/He)F1 (B6C3F1) embryos was injected with monoclonal anti-I-Ek (m alpha I-Ek) antibody every other day starting from the 12th day of gestation. The mixed leukocyte culture reaction (MLR) responses of thymocytes from m alpha I-Ek-treated neonatal mice were assayed against adult B6 (H-2b), C3H/H3 (H-2k) or BALB/c (H-2d) splenic stimulator cells. The syngeneic MLR response of m alpha I-Ek-treated B6C3F1 neonatal thymocytes against C3H stimulator cells was augmented compared to that of untreated neonatal thymocytes. Experiments utilizing recombinant inbred strains of mice as well as monoclonal anti-Ia antibody blocking experiments suggested that the antigen(s) responsible for this augmentation of syngeneic MLR resided in the I-Ek molecule. The MLR response against B6 or BALB/c stimulator cells was not influenced by m alpha I-Ek treatment. We speculate that m alpha I-Ek antibody blocked the expression of I-Ek molecules in B6C3F1 embryos and this resulted in the alteration of T cell self-specificity repertoire in the thymus. Our results support the concept that Ia molecules play important roles for the elimination of self-reactive T lymphocyte clones in the thymus.