Autoreactive T cells from a type I diabetic recognize multiple class II products.

Abstract:

:Mononuclear cells obtained from a child at the acute presentation of type I diabetes were stimulated in vitro with human insulin followed by IL-2 and IL-4. All of the T-cell clones isolated from this stimulation were autoreactive, recognizing autologous B cells in the absence of insulin or other exogenous antigens. Eleven CD4+ clones were studied in detail to identify the class II MHC antigens stimulating these autoreactive cells. The donor was heterozygous for DR3DQw2 and DR4DQw3.2 haplotypes, a combination of alleles with a greatly increased risk for type I diabetes. The clones demonstrated skewed recognition of class II antigens. Three clones appeared to recognize a peptide derived from one class II beta chain (DR beta 1, DR4Dw4) presented by another class II beta chain (DR beta 4, DRw53). Three clones were stimulated by cells expressing DPw4 molecules. Only one clone recognized a product derived from the DR3 haplotype. In contrast to both antigen-specific and autoreactive T-cell clones derived from normal individuals, many of the autoreactive T cells isolated from this subject were stimulated by class II molecules other than DR beta 1. The results support the hypothesis that autoreactive T cells recognize autologous peptides in association with MHC and some of these peptides are derived from self MHC molecules.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Miller G,Nepom GT,Reich MB,Thomas JW

doi

10.1016/0198-8859(93)90128-n

subject

Has Abstract

pub_date

1993-04-01 00:00:00

pages

219-26

issue

4

eissn

0198-8859

issn

1879-1166

pii

0198-8859(93)90128-N

journal_volume

36

pub_type

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