Polymorphisms in MHC class I molecules influence their interactions with components of the antigen processing and presentation pathway

Abstract

MHC class I (MHC‐I) molecules undergo an intricate folding process in order to pick up antigenic peptide to present to the immune system. In recent years, the discovery of a new peptide editor for MHC‐I has added an extra level of complexity in our understanding of how peptide presentation is regulated. On top of this, the incredible diversity in MHC‐I molecules leads to significant variation in the interaction between MHC‐I and components of the antigen processing and presentation pathway. Here, we review our current understanding regarding how polymorphisms in human leukocyte antigen class I molecules influence their interactions with key components of the antigen processing and presentation pathway. A deeper understanding of this may offer new insights regarding how apparently subtle variation in MHC‐I can have a significant impact on susceptibility to disease.

Characterisation of the novel HLA‐A*32:01:01:41 allele by next‐generation sequencing

“…As of March 2024, the IPD‐IMGT/HLA Database has documented a total of 38,975 HLA alleles, of which 8288 are HLA‐A alleles 1 . These molecules are essential for distinguishing between self and non‐self and play a pivotal role in presenting antigens to T cells, thereby initiating immune responses 2 . In this report the identification of the novel HLA‐A*32:01:01:41 allele, is described.…”

“…1 These molecules are essential for distinguishing between self and non-self and play a pivotal role in presenting antigens to T cells, thereby initiating immune responses. 2 In this report the identification of the novel HLA-A*32:01:01:41 allele, is described. It was observed in a 46-year-old Greek female, who was typed for HLA class I and II by NGS technology as volunteer bone marrow donor, during routine typing for HLA class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQB1 and -DPB1), developed at the Immunology and Histocompatibility Dept.…”

Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine

“…For that reason, the region of contact for each allele of the MHC molecule is highly variable, as polymorphic MHC residues will create specific clefts that only certain types of peptide residues can enter. This imposes a very specific binding between the MHC molecule and the peptide and implies that each MHC variant will be able to specifically bind only those peptides that fit properly into the MHC molecule’s cleft, which is variable for each allele [ 39 , 40 ].…”

Associations of functional human leucocyte antigen class I groups with HIV viral load in a heterogeneous cohort

“…Reaching statistical power within this region is difficult and while accounting for the effects of this important immunological region is necessary, it is often ignored altogether. Yet, the function of HLA is conserved as a core component of the immune response [ 8 , 9 ]. This suggests there may be shared functional features within and between populations, even in the presence of genotypic plasticity.…”