Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis

Marco Salvetti, Giovanni Ristori, Mauro D'Amato, Carla Buttinelli, Marika Falcone, Cesare Fieschi, Hartmut Wekerle, Carlo Pozzilli

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Abstract

T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP‐specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant Tcell recognitions of distinct MBP regions were present in three patients, all HLA‐DR2+, independently of the clinical features of their disease. Tcell reactivity was preferentially directed to residues 16‐38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86‐99 was detected in the two other DR2+ patients. In each of the patients with other HLA‐DR haplotypes (DR2), as well as in three DR2+ non‐MS donors, the Tcell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA‐DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA‐DRB1 gene in individuals with the HLA‐DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA‐DR2 gene products alone do not account for the selection of the dominant MBP Tcell epitope.

Original languageEnglish
Pages (from-to)1232-1239
Number of pages8
JournalEuropean Journal of Immunology
Volume23
Issue number6
DOIs
Publication statusPublished - 1 Jan 1993
Externally publishedYes

Keywords

  • HLA typing
  • Multiple sclerosis
  • Myelin basic protein
  • T lymphocytes

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