Immune surveillance for ERAAP dysfunction

详细信息    查看全文

• 作者：Niranjana A. Nagarajan ; Nilabh Shastri ; ^{nshastri@berkeley.edu}
• 关键词：Immune surveillance ; Antigen processing ; MHC class I ; CD8+ T cells
• 刊名：Molecular Immunology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：55
• 期：2
• 页码：120-122
• 全文大小：242 K

文摘

The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1^b, a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1^b complex were frequent in na?ve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1^b complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction.