Activation of a myelin basic protein-specific human T cell clone by antigen-presenting cells from rhesus monkeys

Abstract

This study addresses the capacity of peripheral blood mononuclear cells (PBMC) from rhesus monkeys (Macaca mulatta) to present myelin basic protein (MBP), a candidate auto-antigen for multiple sclerosis, to MBP-specific human CD4+ T cell clones. MHC-restriction of the human T cell clones was determined with HLA-DR-transfected L cells, and epitope specificity was established with a panel of overlapping 20-mer peptides. The MHC-DR region of the rhesus monkeys (Mamu) was characterized serologically and by sequence analysis. We identified one CD4+ HLA-DRB1*0301-restricted Th1-like human T cell clone (ES-BP8) that was activated to proliferation with human or rhesus monkey MBP, or peptide MBP 29-48 presented by PBMC from six different rhesus monkeys expressing the Mamu-DRB1*0305 or -DRB1*0306 alleles. After transformation to continuous growth with Herpesvirus saimiri, the T cell clone could still be stimulated by antigen (Ag) and Ag-presenting cells (APC) from monkeys. Two other T cell clones with the same HLA-restriction and the same peptide-specificity did not respond to MBP presented by these rhesus monkeys. The exon 2 sequences HLA-DRB1*0301, Mamu-DRB1*0305 and -DRB1*0306 differ at positions 32, 47, 67, 73 and 86. These amino acid differences are not critical for the binding of MBP 29-48 and do not abrogate recognition by the clone ES-BP8, but interfere with the recognition of the two other HLA-DRB1*0301-restricted T cell clones. In conclusion, studying Ag-presentation from rhesus monkey may provide further insight into the interaction of antigenic peptide, TCR and MHC.(ABSTRACT TRUNCATED AT 250 WORDS)