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A major influence of the T cell receptor repertoire as compared to antigen processing-presentation in the selection

G Ristori1, C Montesperelli, A Uccelli

  • 1Dipartimento di Scienze Neurologiche, Università La Sapienza, Rome, Italy.

Journal of Neuroimmunology
|May 25, 1999
PubMed

We selected two multiple sclerosis (MS) patients, compatible for HLA-DR2 subtype, and differing for HLA-DM haplotype as well as for the myelin basic protein (MBP) epitope recognized by the vast majority of their T cell lines (TCL) (residues 16-38 and 86-99, respectively). TCL sharing the same restriction element were re-assayed in the presence of reciprocally mismatched antigen-presenting cells (APC). The TCL recognized both the whole MBP and the relevant peptide also in the presence of non-autologous APC, (compatibility for processing, despite a difference in the DM haplotype). The same protocol, performed in serum-free pulsing experiments or in the presence of 'fixed' APC, excluded extracellular processing or mutual T cell presentation, and confirmed the need for MBP processing in our system. The finding, that only TCL recognizing MBP peptide 16-38 (a region not previously related to the DR2 haplotype) used a novel Vbeta, supports the importance of the TCR repertoire over the processing-presentation machinery in the selection of MBP epitopes in MS.

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