THE INFLUENCE OF MHC POLYMORPHISM ON THE SELECTION OF T-CELL DETERMINANTS OF FMDV IN CATTLE

There is a quest for the development of a new generation of vaccines c onsisting of well-defined subunit antigens. For a number of practical reasons it is attractive to develop vaccines on the basis of synthetic peptides. However, their efficacy may be limited by genetic restricti ons imposed on T-cell recognition via major histocompatibility complex (MHC) polymorphism, as shown by many studies using inbred animal spec ies. To study the effect of MHC polymorphism in an outbred species, we selected four cattle homozygous for different A-DR-DQ haplotypes, and another four cattle which shared one haplotype in combination with a haplotype of one of the MHC homozygous animals. We analysed responses to synthetic peptides comprising defined T-cell epitopes of foot-and-m outh disease virus (FMDV) in this selected group of FMDV-vaccinated ca ttle. This analysis shows that even in outbred animals, MHC polymorphi sm in influences the responses to synthetic peptides. Interestingly, o ne of the peptides, VP4[20-34], was recognized in association with at least four different MHC haplotypes. Fine specificity analysis of this peptide revealed subtle shifts in the core epitope recognized. All pe ptides that induced lymphocyte proliferation in vitro were found to in duce a T-helper type-1 (Th1) type of response, irrespective of the MHC haplotype involved. Together, these data support the notion that indi viduals carrying distinct MHC types can be vaccinated successfully by vaccines that include only a limited number of peptides. In the design of a peptide vaccine against FMDV we suggest inclusion of the highly conserved VP4 sequence 20-34.