HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals

Dolores Jaraquemada, Roland Martin, Sandra Rosen-Bronson, Marjorie Flerlage, Henry F. McFarland, Eric O. Long

Research output: Contribution to journalArticlepeer-review

Abstract

The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRa and either DR2a or DR2b β-chain cDNA. DR2a and DR2b represent the two isotypic DRβ chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but, rather, to the binding of different MBP peptides to DR2a molecules.

Original languageEnglish (US)
Pages (from-to)2880-2885
Number of pages6
JournalJournal of Immunology
Volume145
Issue number9
StatePublished - Nov 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals'. Together they form a unique fingerprint.

Cite this