No evidence of an influence of the noninherited maternal HLA antigens on the alloreactive T cell repertoire in healthy individuals.

In order to test whether a selective T cell nonresponsiveness to noninherited maternal human leukocyte antigens (NIM) exists, we measured the frequencies of alloreactive T cells of healthy individuals to their NIM HLA antigens and to their noninherited paternal (NIP) HLA antigens by limiting dilution assays. Both the frequencies of cytotoxic T cell precursors (CTLp) and IL-2-producing helper T cell precursors (HTLp) were determined. Similar frequencies were observed for NIM class I-reactive CTLp and NIP class I-reactive CTLp. This was the case when frequencies were determined against total NIM and NIP haplotypes but also when CTLp frequencies against individual NIM and NIP antigens were measured. A positive finding of this study was the confirmation of our earlier observation that CTLp frequencies against individual HLA-A antigens are generally lower than CTLp frequencies against HLA-B. This was found both for the maternal and the paternal HLA-A and -B antigens. Similarly, comparable frequencies of IL-2-producing helper T cell precursors directed against NIM HLA class II antigens and NIP HLA class II antigens were found. When breast-feeding in the neonatal period was considered, no differences in the frequencies of CTLp and HTLp were observed between children who had been breast-fed and children who had not. Therefore the present data do not support the hypothesis that confrontation with noninherited maternal HLA in neonatal life leads to down-regulation of alloreactive T cell responses to the mother.