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Altered Allogeneic Response in Neonatally Anti‐MHC Class I‐Treated Mice

Neonatal treatment of C3H mice (H‐2k) with anti‐Kk monoclonal antibodies results in altered cytotoxic responses against allogeneic targets. 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 significantly reduced cytotoxic response against various allogeneic major histocompatibility complex (MHC) class I‐expressing targets. The strongest reduction was observed in very young mice (up to 2 weeks of age). As 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 reduces alloreactivity and most likely also the diversity of TCR‐repertoire. However, the reduced alloresponsiveness was not restricted to either allogeneic K‐ or D‐encoded molecules, suggesting that self MHC‐D‐region encoded molecules can mediate positive selection of T cells able to react against both K and D region‐encoded allogeneic MHC class I molecules.