About the Special Issue

Human leukocyte antigen (HLA) plays a critical early role in the human immune response to foreign antigens such as viruses and bacteria and has been widely implicated in conferring risk for, or protection against, development of various health conditions. HLA genes code for cell-surface HLA molecules that bind with and present peptides of foreign antigen proteins to T cells, stimulating cellular and humoral immune system responses aimed at elimination of foreign antigens. Successful immune system responses to foreign antigens depends on binding affinity and immunogenicity of the peptide-HLA complex. However, HLA is the most highly polymorphic region of the human genome and even single amino acid differences in HLA alleles affect binding affinity and immunogenicity. In the case of HLA-peptide mismatch in which binding affinity and/or immunogenicity is low, foreign antigens may persist, contributing to chronic health conditions. Indeed, recent evidence points to the persistence of SARS-CoV-2 antigen in long-COVID, and other persistent antigens have been associated with chronic conditions including Lyme disease, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Gulf War Illness/Chronic Multisymptom Illness, among others. For various other chronic conditions, HLA has been implicated although evidence of antigen persistence is limited. The premise of this special issue is that HLA influences risk for chronic conditions via its role in foreign antigen elimination. As such, contributions related to HLA, chronic conditions, foreign antigen exposure and persistence, and their interrelationships are well-suited for this special issue.

Keywords: Immunogenetics; Human Leukocyte Antigen (HLA); Chronic Ilnesses

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