Deciphering Human Leukocyte Antigen Susceptibility Maps From Immunopeptidomics Characterization in Oncology and Infections

Abstract

Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to many diseases such as cancer, auto-immune or infectious diseases. Individual genetic variation may help to explain different immune responses to microorganisms across a population. HLA typing can be fast and inexpensive; however, deciphering peptides loaded on MHC-I and II which are presented to T cells, require the design and development of high-sensitivity methodological approaches and subsequently databases. Hence, these novel strategies and databases could help in the generation of vaccines using these potential immunogenic peptides and in identifying high-risk HLA types to be prioritized for vaccination programs. Herein, the recent developments and approaches, in this field, focusing on the identification of immunogenic peptides have been reviewed and the next steps to promote their translation into biomedical and clinical practice are discussed.

SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS

“…It has been suggested that some MHC molecules can present viral peptides with epitopes very similar to their own peptides, which may lead to the activation of autoreactive T cells. Variations in the MHC locus are also closely related to many different autoimmune diseases (7,45,46) given dysregulation, identification of AABs in COVID-19 and its associated pathologies, as we have observed in our results, have also been demonstrated in other studies about the diversity (47), frequency and suggested function of these AABs (48).…”

“…In this regard, our results show AABs previously described as a function of pathology severity related to tissue and vascular damage such as MOK1 (50), antigenic proteins associated with lung damage such as MUC1 (51) including pro-inflammatory and inflammatory cytokines such as TNF, and interleukins like CXCL8 involved in the cytokine cascade and related with sepsis and septic shock (37,52). In addition, our results show a higher amount of AABs in patients with advanced age as demonstrated in studies of other autoimmune pathologies as there is an enhancement of autoimmunity in immunosenescence development (53)(54)(55)(56). Overall, these results show an AAB profile that discriminate ± ARDS patients and their severity (Figures S8, S9).…”

“…With regards to the adaptive response, serum antibodies are essential components of specific immunity but are also involved in the pathogenesis of many autoimmune diseases, allergies, and oncopathologies. While a lot is known about the mechanism of host antibody production following pathogen or infectious exposure or vaccination, the induction of autoantibodies (AABs) in many other diseases still remains to be clearly elucidated (7,8).…”

Challenges of Rabies Serology: Defining Context of Interpretation

“…Studies have shown response to vaccination is dependent on an individual’s immune system genes, which can vary considerably, inspiring new vaccine development into targeting antigen epitopes to specific human leukocyte antigen (HLA) genes [ 54 , 55 , 56 ]. The recognition of high and low responders was noted by Kuwert et al in 1981, identifying high responders as those with early and high RVNA titer responses compared to lower titers and later peaks in low responders [ 57 ].…”

Single-Cell Proteomics: The Critical Role of Nanotechnology

“…Several human health situations are related to disturbances of the immune system (autoimmune diseases, infectious diseases, or chronic inflammation) and other pathologies with different ontogeny (i.e., cancer, neurodegenerative disorders) [ 14 ]. Recently, it was described that approximately 20% of cancers (solid tumors and onco-hematological pathologies) can be caused by infectious agents, with Helicobacter pylori , hepatitis C virus, or Kaposi’s sarcoma-associated herpesvirus being some examples [ 15 , 16 ]. Novel therapeutic approaches for the treatment of tumors have emerged as a consequence of the close relationship between the immune system and the different diseases.…”