ALTERED ALLOGENEIC RESPONSE IN NEONATALLY ANTI-MHC CLASS I-TREATED MICE

Neonatal treatment of C3H mice (H-2(k)) with anti-K-k monoclonal antib odies results in altered cytotoxic responses against allogeneic target s. After 2-3 weeks of antibody treatment, no difference in the number of CD4(+)8(-) or CD4(-) 8(+) T cells was observed between the antibody - and saline-treated mice. However, antibody-treated mice had a signif icantly reduced cytotoxic response against various allogeneic major hi stocompatibility complex (MHC) class I-expressing targets. The stronge st reduction was observed in very young mice (up to 2 weeks of age). A s the mice got older, the allo MHC-specific responses reached control levels. No significant changes in T-cell receptor (TCR)-V-region usage was observed even in young antibody-treated mice. The results suggest that the reduction in the number of positively selecting elements red uces alloreactivity and most likely also the diversity of TCR-repertoi re. However, the reduced alloresponsiveness was not restricted to eith er allogeneic K- or D-encoded molecules, suggesting that self MHC-D-re gion encoded molecules can mediate positive selection of T cells able to react against both K and D region-encoded allogeneic MHC class I mo lecules.