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Effects of C2ta genetic polymorphisms on MHC class II expression and autoimmune diseases
Author(s) -
Yau Anthony C. Y.,
Piehl Fredrik,
Olsson Tomas,
Holmdahl Rikard
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12692
Subject(s) - ciita , major histocompatibility complex , biology , mhc class ii , antigen presentation , experimental autoimmune encephalomyelitis , antigen processing , immunology , mhc class i , mhc restriction , autoimmunity , immune system , t cell
Summary Antigen presentation by the MHC ‐ II to CD 4 + T cells is important in adaptive immune responses. The class II transactivator ( CIITA in human and C2 TA in mouse) is the master regulator of MHC ‐ II gene expression. It coordinates the transcription factors necessary for the transcription of MHC ‐ II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC ‐ II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC ‐ II haplotype H‐2 q ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC ‐ II expression and function. We demonstrate that an allelic variant in the type I promoter of C2ta resulted in an increased expression of MHC ‐ II on macrophages (72–151% higher mean florescence intensity) and conventional dendritic cells (13–65% higher mean florescence intensity) in both spleen and peripheral blood. The increase in MHC ‐ II expression resulted in an increase in antigen presentation to T cells in vitro and increased T‐cell activation. The differential MHC ‐ II expression in B6Q. C2ta , however, did not alter the disease development in models of rheumatoid arthritis (collagen‐induced arthritis and human glucose‐6‐phosphate‐isomerase 325–339 ‐peptide‐induced arthritis), or multiple sclerosis ( MOG 1–125 protein‐induced and MOG 79–96 peptide‐induced experimental autoimmune encephalomyelitis). This is the first study to address the role of an allelic variant in type I promoter of C2ta in MHC ‐ II expression and autoimmune diseases; and shows that C2ta polymorphisms regulate MHC ‐ II expression and T‐cell responses but do not necessarily have a strong impact on autoimmune diseases.