The hypothesis that mimicry between a self and a microbial peptide antigen is strictly related to autoimmune pathology remains a debated concept in autoimmunity research. Clear evidence for a causal link between molecular mimicry and autoimmunity is still lacking. In recent studies we have demonstrated that viruses and bacteria share amino acid sequences with the human proteome at such a high extent that the molecular mimicry hypothesis becomes questionable as a causal factor in autoimmunity. Expanding upon our analysis, here we detail the bacterial peptide overlapping to the human proteome at the penta-, hexa-, hepta- and octapeptide levels by exact peptide matching analysis and demonstrate that there does not exist a single human protein that does not harbor a bacterial pentapeptide or hexapeptide motif. This finding suggests that molecular mimicry between a self and a microbial peptide antigen cannot be assumed as a basis for autoimmune pathologies. Moreover, the data are discussed in relation to the microbial immune escape phenomenon and the possible vaccine-related autoimmune effects.

Background: Peptides derived from endogenous antigens can bind to MHC class I molecules. Those which bind with high affinity can invoke a CD8 + immune response, resulting in the destruction of infected cells. Much work in immunoinformatics has involved the algorithmic prediction of peptide binding affinity to various MHC-I alleles. A number of tools for MHC-I binding prediction have been developed, many of which are available on the web.

Major histocompatibility complex class I genes are among the most polymorphic genes characterized. The high level of polymorphism is essential for generating host immune responses. In humans, three distinct genomic loci encode human leukocyte antigen (HLA) class I genes, allowing individuals to express up to six different HLA class I molecules. In cattle, the number of distinct genomic loci are currently at least six, and the number of different bovine leukocyte antigens (BoLA) class I molecules that are expressed in individual animals are variable. The extent of allele variation within the cattle population is unknown. In this study, the number and variety of BoLA class I sequences expressed by 36 individuals were determined from full-length BoLA class I cDNA clones. Twenty distinct BoLA class I alleles were identified, with only four being previously reported. The number of expressed BoLA class I alleles in individual animals ranged between one and four, with none of the animals having an identical complement of BoLA class I molecules. Variation existed in the number of BoLA class I alleles expressed as well as the composition of expressed alleles, however, several BoLA class I alleles were found in multiple individual animals. Polymorphic amino acid sites were analyzed for positive and negative selection using the ADAPTSITE program. In the antigen recognition sites (ARS), there were eight positions that were predicted to be under positive selection and three positions that were predicted to be under negative selection from 62 positions. In contrast, for non-antigen recognition sites (non-ARS), there were three positions that were predicted to be under positive selection and 20 that were predicted to be under negative selection from 278, indicating that positive selection of amino acids occurs at a greater frequency within the antigen recognition sites.

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