Melanoma and Human Leukocyte Antigen (HLA): Immunogenicity of 69 HLA Class I Alleles With 11 Antigens Expressed in Melanoma Tumors.

Host immunogenetics play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes that stimulate T cell response hinge on binding affinity and immunogenicity of human leukocyte antigen (HLA) with melanoma antigen epitopes. Here, we use an in silico approach to characterize binding affinity and immunogenicity of 69 HLA Class I human leukocyte antigen alleles to epitopes of 11 known melanoma antigens. The findings document a significant proportion of positively immunogenic epitope-allele combinations, with the highest proportions of positive immunogenicity found for the Q13072/BAGE1 melanoma antigen and alleles of the HLA B and C genes. The findings are discussed in terms of a personalized precision HLA-mediated adjunct to immune checkpoint blockade immunotherapy to maximize tumor elimination.

Schizophrenia, Human Leukocyte Antigen (HLA), and Herpes Viruses: Immunogenetic Associations at the Population Level.

Several factors have been implicated in schizophrenia (SZ), including human herpes viruses (HHV) and the adaptive immunity Human Leukocyte Antigen (HLA) genes. Here we investigated these issues in 2 complementary ways. In one analysis, we evaluated SZ-HLA and HHV-HLA associations at the level of a single allele by computing (a) a SZ-HLA protection/susceptibility (P/S) score based on the covariance between SZ and 127 HLA allele prevalences in 14 European countries, (b) estimating in silico HHV-HLA best binding affinities for the 9 HHV strains, and (c) evaluating the dependence of P/S score on HHV-HLA binding affinities. These analyses yielded (a) a set of 127 SZ-HLA P/S scores, varying by >200× (maximum/minimum), which could not be accounted for by chance, (b) a set of 127 alleles × 9 HHV best-estimated affinities, varying by >600×, and (c) a set of correlations between SZ-HLA P/S scores and HHV-HLA binding which indicated a prominent role of HHV1. In a subsequent analysis, we extended these findings to the individual person by taking into account the fact that every individual carries 12 HLA alleles and computed (a) the average SZ-HLA P/S scores of 12 randomly chosen alleles (2 per gene), an indicator of HLA-based SZ P/S for an individual, and (b) the average of the corresponding HHV estimated affinities for those alleles, an indicator of overall effectiveness of HHV-HLA binding. We found (a) that HLA protection for SZ was significantly more prominent than susceptibility, and (b) that protective SZ-HLA scores were associated with higher HHV-HLA binding affinities, indicating that HLA binding and subsequent elimination of several HHV strains may confer protection against schizophrenia.

SARS-CoV-2 in silico binding affinity to human leukocyte antigen (HLA) Class II molecules predicts vaccine effectiveness across variants of concern (VOC).

There is widespread concern about the clinical effectiveness of current vaccines in preventing Covid-19 caused by SARS-CoV-2 Variants of Concern (Williams in Lancet Respir Med 29:333-335, 2021; Hayawi in Vaccines 9:1305, 2021), including those identified at present (Alpha, Beta, Gamma, Delta, Omicron) and possibly new ones arising in the future. It would be valuable to be able to predict vaccine effectiveness for any variant. Here we offer such an estimate of predicted vaccine effectiveness for any SARS-CoV-2 variant based on the amount of overlap of in silico high binding affinity of the variant and Wildtype spike glycoproteins to a pool of frequent Human Leukocyte Antigen Class II molecules which are necessary for initiating antibody production (Blum et al. in Annu Rev Immunol 31:443-473, 2013). The predictive model was strong (r = 0.910) and statistically significant (P = 0.013).

Vaccines for Influenza.

Two reviews by Harding and Heaton [...].