Potential role of HLA alleles in viral infections. Inpact of HLA genotypes on antigen presentation in T cell - mediated immune response.

Viral infections are socially important infectious diseases and are widespread in the human population. In response to viral infections, complex mechanisms of innate and adaptive immunity are activated, in which the immune response from lymphoid T-cells plays a crucial role. The major signal for T-cell activation is the recognition of a processed viral peptide-antigen in the context of the major histocompatibility complex (MHC), which in case of the human population is called HLA: HLA class I molecules (present antigens to CD8+ T-lymphocytes) and HLA class II molecules (present antigens to CD4+ T-lymphocytes). The effectiveness of the T-cell-mediated adaptive immune response to viral infection depends on the quality of presentation and recognition of antigen peptides. The working hypothesis of the study is to try to identify those combinations of "virus – HLA allele", for which the estimated efficacy of presentation of viral peptides by a given allele will have maximum or minimum values, assuming that in such case the value of the potential T-cell component of the immune response will also have maximum / minimum values. This will help to identify patients for whom the course of the disease is predicted to be the most mild / severe based on HLA-typing, all other things being equal. The universal coefficients of viral antigens presentation by HLA alleles were calculated as a result of the study: 61 proteomes of the most common or the most dangerous viruses, 87 HLA-I alleles and 235 two-locus HLA-II haplotypes forming a peptide-binding groove, 46 three-locus haplotypes of HLA class I alleles and 34 haplotypes of HLA class II alleles were considered. The following conclusions can be drawn from the obtained results: – viral proteins, as has been considered, are presented by different HLA alleles with varying effectiveness, both protective and risk alleles and haplotypes are distinguished for each of the viruses; – antigens of a number of viruses are presented with extremely high (or low) efficacy by certain HLA alleles, while over viruses can be characterized by less variety in presentation; – some viruses are presented by certain HLA class II alleles with an affinity below the threshold; – differences in the level of viral peptides presentation by MHC-I and MHC-II molecules have been identified: some viruses are better represented by the MHC-II alleles and worse by the MHC-I alleles, and vice versa. The obtained data of viral presentation coefficients can be used not only to predict the severity of a viral disease for a particular patient with identified HLA haplotypes, but also to better understand the processes of epidemic progression in large populations. For example, it will help to adjust the parameters of classical SIR-models and their modifications when building dynamic models of the epidemic growth in a certain area. The results can also be used in the development of antiviral vaccines to identify the most immunogenic fragments of viral proteomes, fragments of viral proteins that contain the maximum number of peptides with high binding affinity for chosen HLA alleles.