Direct Evidence for Functional Self-protein/Ia-molecule Complexes in Vivo

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1988 Jul 1

PMID 2839836

Citations 31

Authors

R G Lorenz

P M Allen

Affiliations

Soon will be listed here.

Abstract

Through the development of a panel of murine hybridomas reactive to murine hemoglobin, we have been able to study the processing and presentation of self antigens by antigen-presenting cells. Our results demonstrate that peritoneal macrophages in vivo can process and potentially present the self-antigen hemoglobin. We have extended this finding to show that, directly after removal from the mouse, antigen-presenting cells from a variety of tissues stimulate our hemoglobin-specific hybridomas without any manipulation or addition of exogenous antigen. This constitutes direct functional proof that in a nondisease state self proteins are processed constitutively and can be presented in a fashion similar to that in which foreign antigens are presented. Our demonstration that antigen-presenting cells can process and potentially present self as well as foreign molecules implies that self-tolerance occurs at the level of the T cell. This constitutive processing and presentation of self antigens has potentially far-reaching implications in self-tolerance, autoimmunity, and alloreactivity.

Citing Articles

Self-pMHCII complexes are variably expressed in the thymus and periphery independent of mRNA expression but dependent on the activation state of the APCs.

Rodriguez S, Jiang M, Bujo H, Allen P Mol Immunol. 2014; 63(2):428-36.

PMID: 25451972 PMC: 4254551. DOI: 10.1016/j.molimm.2014.09.016.

Self-awareness: how self-peptide/MHC complexes are essential in the development of T cells.

Lo W, Allen P Mol Immunol. 2012; 55(2):186-9.

PMID: 23196128 PMC: 3594560. DOI: 10.1016/j.molimm.2012.10.028.

Self heat-shock protein 65-mediated regulation of autoimmune arthritis.

Durai M, Huang M, Moudgil K J Autoimmun. 2009; 33(3-4):208-13.

PMID: 19800761 PMC: 3389818. DOI: 10.1016/j.jaut.2009.09.007.

Initiation of an autoimmune response: insights from a transgenic model of rheumatoid arthritis.

Mandik-Nayak L, Allen P Immunol Res. 2005; 32(1-3):5-13.

PMID: 16106055 DOI: 10.1385/IR:32:1-3:005.

Self determinant selection and acquisition of the autoimmune T cell repertoire.

Benichou G, Tam R, Orr P, Garovoy M, Fedoseyeva E Immunol Res. 1996; 15(3):234-45.

PMID: 8902578 DOI: 10.1007/BF02918251.

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