Induction of effective cross-reactive immunity by FMDV peptides is critically dependent upon specific MHC-peptide-T cell interactions.

BoCD4+ T-cell clones specific for a peptide derived from foot-and-mouth disease virus envelope protein, VP1 (FMDV15) were generated from two responder cattle. One animal was a high and the other was an intermediate responder in terms of both T-cell and antibody responses. However both animals had identical major histocompatibility complex (MHC) class II DR-like types (DRBF3,6) according to a one-dimensional isoelectric focusing method which distinguishes DR-like alleles. In contrast, mixed lymphocyte reaction (MLR) responses indicated that they shared only one haplotype (DRBF3) and anti-DRBF6 alloclones also differentiated between the animals. This suggested that the animals differed at a non-DR-like locus. Restriction patterns of FMDV-specific clones derived from these animals indicated that FMDV15 was presented by the non-DR-like class II molecules associated with DRBF6. Only one clone, derived from the high responder animal, was restricted to DRBF3. Thus products from the non-DR-like locus (probably DQ-like) are functionally important for presentation of FMDV peptides. Furthermore the allelic differences detected by the alloclones are also critical for peptide binding. The majority of clones from the high responder animal recognized an immunodominant region containing a Rothbard epitope whereas none of the clones from the intermediate responder did so. This suggests that the region recognized by T cells, which is dependent upon MHC type, influences the B-cell response and thus the degree of protection obtained. This has major implications for rational vaccine design involving T- and B-cell epitopes.