HLA-C*05:311, a novel HLA class I allele detected by next-generation sequencing.
HLA-C*05:311, a novel HLA class I allele detected by next-generation sequencing.
HLA-DQB1*05:367 differs from HLA-DQB1*05:01:01:01 by one nucleotide substitution in codon 7 in exon 2.
Alloreactivity entails the recognition of cells and tissues from one individual as foreign by T cells and other immune effectors from another individual. Alloreactive immune responses play an important role in various clinical contexts, in particular in transplantation. Major drivers of these responses are the highly immunogenic, non-self HLA molecules. However, the immunogenicity of these allogeneic HLA molecules has been observed to vary according to certain immunobiological and immunogenetic parameters, leading to the concept of differential alloreactivity. Recent progress in unveiling the underpinnings of this phenomenon has been made for the frequently mismatched HLA-DP allotypes, whose singular genomic, structural and population genetics characteristics offer an ideal scenario for these investigations. Studies in the HLA-DP context have highlighted the immunopeptidome overlap between self and non-self HLA allotypes, as well as its editing by non-classical class II chaperones HLA-DM and HLA-DO, as a main determinant of their immunogenicity likely via indirect effects of thymic education. Recent evidence suggests that these observations could also be extended to alloresponses directed against HLA molecules encoded by other loci. How these functional characteristics of HLA molecules shape allorecognition by T-cell subsets, and how they translate into different clinical consequences in the context of transplantation will be the subject of the present review.
HLA-F*01:31 differs from HLA-F*01:04:01 by one nonsynonymous nucleotide substitution in codon 183 in exon 3.
HLA-DQA1*03:02:05 differs from HLA-DQA1*03:02:01:01 by one nucleotide substitution at position 639 located in exon 4.
HLA-A*02:540:02N differs from A*02:01:01:01 by one nucleotide substitution in codon 99 in exon 3.
One nucleotide substitution in codon 133 of HLA-DQB1*03:03:02:01 results in a novel allele HLA-DQB1*03:319.
Single molecule real-time sequencing identifies the novel recombinant allele HLA-DPB1*01:01:01:31.
The novel HLA-DQB1*04:107 allele differs from DQB1*04:01:01:03 by a change of A>G in exon 2.
COVID-19 is a respiratory disease caused by SARS-CoV-2, in which severe outcomes are primarily driven by an exacerbated immune response. The HLA region has been extensively investigated in COVID-19 due to its central role in the immune response, although genetic associations vary across populations. Here, the association of HLA genetic variability with COVID-19 severe respiratory outcomes was investigated in an admixed population from Rio de Janeiro, Brazil. Results of a comparative study between mild and severe COVID-19 cases involving 306 individuals have suggested risk associations with severe COVID-19 for the HLA-DPB1*13:01 allele (OR = 3.42, 95% CI = 1.05–11.16, p = 0.041) and the HLA-B*39 allele group (OR = 3.26, 95% CI = 1.16–9.13, p = 0.024), although statistical significance was lost after FDR adjustment for multiple comparisons (adjusted p > 0.05). Amino acid analyses showed that a serine at position 116 of HLA-B conferred protection against severe COVID-19 (OR = 0.4774, 95% CI = 0.28–0.81, p = 0.006, adjusted p = 0.031). In silico analysis using the NetMHCpan tool predicted that this residue, located in the HLA-B peptide-binding groove, has enhanced binding affinity to immunodominant SARS-CoV-2 epitopes, suggesting a functional mechanism underlying the observed protection. The association of single nucleotide variants at the HLA region was also investigated, and no statistically significant association was found. Results obtained in the present study underscore the importance of HLA in COVID-19 severity, likely mediated by its influence on viral peptide presentation, and advance our understanding of the genetic underpinnings of severe disease in admixed populations.
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