A major influence of the T cell receptor repertoire as compared to antigen processing-presentation in the selection of myelin basic protein epitopes in multiple sclerosis.
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.
Ristori
G
G
Dipartimento di Scienze Neurologiche, Università La Sapienza, Rome, Italy.
Montesperelli
C
C
Uccelli
A
A
Giunti
D
D
Buttinelli
C
C
Bomprezzi
R
R
Mancardi
G L
GL
Salvetti
M
M
D000938:Antigen-Presenting Cells / Q000502:physiology*; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta