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

This study addresses the capacity of peripheral blood mononuclearcells (PBMC) from rhesus monkeys (Macaca mulatta) to presentmyelin basic protein (MBP), a candidate auto-antigen for multiplesclerosis, to MBP-speclfic human CD4⁺ T cell clones. MHC-restrictlonof the human T cell clones was determined with HLA-DR-transfectedL cells, and epitope specificity was established with a panelof overlapping 20-mer peptides. The MHC-DR region of the rhesusmonkeys (Mamu) was characterized serologlcally and by sequenceanalysis. We identified one CD4⁺ HLADRB1*0301-restrlcted T_h1-llkehuman T cell clone (ES-BP8) that was activated to proliferationwith human or rhesus monkey MBP, or peptide MBP 29–48presented by PBMC from six different rhesus monkeys expressingthe Mamu-DRB1*0305 or -DRB1*0306 alleles. After transformationto continuous growth with Herpesvirus salmiri, the T cell clonecould still be stimulated by antigen (Ag) and Ag-presentlngcells (APC) from monkeys. Two other T cell clones with the sameHLA-restriction and the same peptide-specificity did not respondto MBP presented by these rhesus monkeys. The exon 2 sequencesHLA-DRB1*0301, Mamu-DRBV^*0305 and -DRB 1* 0306 differ at positions32, 47, 67, 73 and 86. These amino acid differences are notcritical for the binding of MBP 29–48 and do not abrogate-recognitionby the clone ES-BP8, but interfere with the recognition of thetwo other HLA-DRB1^*0301-restricted T cell clones. In conclusion,studying Ag-presentation from rhesus monkey may provide furtherinsight Into the Interaction of antigenic peptide, TCR and MHC.Furthermore, these results could form a useful basis for theIn vivo transfer of human auto-Ag-specific T cells into rhesusmonkey recipients.