Bovine T cells recognize antigen in association with MHC class II haplotypes defined by one-dimensional isoelectric...

A recently established, one-dimensional isoelectric focusing (IEF) method for distinguishing major histocompatibility complex (MHC) class II polymorphisms in an outbred species, cattle, has allowed us to analyse the involvement of the MHC in the recognition of antigen by bovine T cells. Bovine T-cell lines of Th cell phenotype (BoCD4+) specific for ovalbumin were generated from six individual high responder animals. These animals were bovine MHC (BoLA) class II typed using the IEF technique which detects bovine DR-like products. Four of the animals were shown to be heterozygous and two were homozygous for the IEF specificities. Six out of the 13 IEF specificities (EDF types) detected so far were represented by this group of animals. The cell lines were tested against a panel of IEF-typed antigen-presenting cells (APC) from unrelated donors. The lines only responded to antigen in proliferation assays when the APC shared at least one MHC class II EDF specificity with the BoCD4+ cell line. The responses did not correlate with BoLA class I specificities. However, lines from one of the animals were consistently generated to one of the two haplotypes only. This suggests that there are non-responder alleles to a multi-epitope antigen, present in the cattle population. The results demonstrate that IEF of bovine MHC class II products defines haplotypes of functional relevance, and may indeed be identifying the actual restriction elements involved in presentation of ovalbumin. These results have important implications for future vaccine design in an outbred species, particularly in terms of immune response gene effects and disease associations.