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  2. Minor histocompatibility protein HMSD variant form

Minor histocompatibility protein HMSD variant form

Definition:

This splice variant of HMSD is the precursor of the histocompatibility antigen ACC-6. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. However, associated with GVHD, a favorable graft-versus-leukemia (GVL) can be induced by donor-recipient disparities in mHags. ACC-6 is presented to the cell surface by MHC HLA-B*4403. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. Immunogenicity of most autosomal mHags results from single-nucleotide polymorphisms that cause amino-acid substitutions within epitopes, leading to the differential recognition of peptides between donor and recipient.

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