Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity

A. J. Slavin, J. M. Soos, O. Stuve, J. C. Patarroyo, H. L. Weiner, A. Fontana, E. K. Bikoff, S. S. Zamvil

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Abstract

The role of processing in antigen (Ag) presentation and T cell activation in experimental allergic encephalomyelitis (EAE) was evaluated in wild-type mice, mice that selectively express either Ii p31 or p41, and mice completely deficient in Ii or H-2M. We demonstrate that processing of myelin oligodendrocyte glycoprotein (MOG) is required for presentation of the dominant encephalitogenic MOG epitope, p35-55. Ii p31- and p41-expressing mice developed EAE with similar incidence to wild-type mice, although p41 mice had a more severe course. Ag-presenting cells (APCs) from Ii- or H-2M-deficient mice could present p35-55, but not MOG, demonstrating that these APCs could not process native MOG. Ii- and H-2M-deficient mice were not susceptible to EAE by immunization with p35-55 or MOG or by adoptive transfer of encephalitogenic T cells. However, CD4+ T cells from p35-55-immunized H-2M-deficient mice proliferated, secreted IFN-γ, and transferred EAE to wild-type, but not H-2M-deficient, mice. Thus, EAE resistance in H-2M-deficient mice is not due to an inability of APCs to present p35-55, or an intrinsic defect in the encephalitogenic T cell repertoire, but reflects a defect in APC function. Our results indicate that processing is required for initial Ag presentation and CNS T cell activation and suggest that autopathogenic peptides of CNS autoantigen may not be readily available for presentation without processing.

Original languageEnglish (US)
Pages (from-to)1133-1139
Number of pages7
JournalJournal of Clinical Investigation
Volume108
Issue number8
DOIs
StatePublished - 2001

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Antigen Presentation
Autoimmunity
Myelin-Oligodendrocyte Glycoprotein
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
invariant chain
Adoptive Transfer
Autoantigens
Antigen-Presenting Cells
Epitopes
Immunization
Peptides

ASJC Scopus subject areas

  • Medicine(all)

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Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. / Slavin, A. J.; Soos, J. M.; Stuve, O.; Patarroyo, J. C.; Weiner, H. L.; Fontana, A.; Bikoff, E. K.; Zamvil, S. S.

In: Journal of Clinical Investigation, Vol. 108, No. 8, 2001, p. 1133-1139.

Research output: Contribution to journalArticle

Slavin, A. J. ; Soos, J. M. ; Stuve, O. ; Patarroyo, J. C. ; Weiner, H. L. ; Fontana, A. ; Bikoff, E. K. ; Zamvil, S. S. / Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 8. pp. 1133-1139.
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