The Immune Response Under Stress Class I Hla Presentation Of Hostderived Peptides


1The Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 USA

2 The Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas USA

Abstract: Major histocompatibility complex (MHC) class I molecules are found at the surface of all nucleated cells. Class I molecules function as immune sentries by scanning the intracellular proteome and then reflecting the proteome at the cell surface. Through class I presented peptides, T lymphocytes and other immune effector cells can continuously survey the intracellular proteome. Viral infection and cancerous transformation results in the presentation of peptides not found on healthy cells. Class I presented peptides therefore act to distinguish infected and cancerous cells in the eyes of the immune response. Here, we review how class I molecules reflect host cell stress resulting from infection and cancerous transformation. Class I molecules display peptides derived from heat shock proteins on both cancerous and virus-infected cells, and these peptides are clearly recognized by the immune response. The class I of diseased cells also reveal less obvious stress-related signals: Peptide fragments of proteins involved in cell homeostasis act to distinguish infected or cancerous cells. Finally, peptides derived from particular host proteins act as broad indicators of cellular stress, distinguishing both cancerous and virus-infected cells. These class I presented peptides are positioned to influence adaptive and innate immune responses to cellular stress

Keywords: HLA class I molecule; MHC class I molecule; stress; virus; cancer; heat shock protein

•University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC Room 317, Oklahoma City, Oklahoma 73104, Tel.: (405) 271-1203, Fax.: (405) 271-3874, [email protected]

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