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Major histocompatibility complex class I diversity limits the repertoire of T cell receptors.

ABSTRACT: Major histocompatibility complex (MHC) genes encode proteins that initiate adaptive immune responses through the presentation of foreign antigens to T cells. The high polymorphism found at these genes, thought to be promoted and maintained by pathogen-mediated selection, contrasts with the limited number of MHC loci found in most vertebrates. Although expressing many diverse MHC genes should broaden the range of detectable pathogens, it has been hypothesized to also cause deletion of larger fractions of self-reactive T cells, leading to a detrimental reduction of the T cell receptor (TCR) repertoire. However, a key prediction of this TCR depletion hypothesis, that the TCR repertoire should be inversely related to the individual MHC diversity, has never been tested. Here, using high-throughput sequencing and advanced sequencing error correction, we provide evidence of such an association in a rodent species with high interindividual variation in the number of expressed MHC molecules, the bank vole (Myodes glareolus). Higher individual diversity of MHC class I, but not class II, was associated with smaller TCR repertoires. Our results thus provide partial support for the TCR depletion model, while also highlighting the complex, potentially MHC class-specific mechanisms by which autoreactivity may trade off against evolutionary expansion of the MHC gene family.

SUBMITTER: Migalska M

PROVIDER: S-EPMC6421458 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Major histocompatibility complex class I diversity limits the repertoire of T cell receptors.

Migalska Magdalena M Sebastian Alvaro A Radwan Jacek J

Proceedings of the National Academy of Sciences of the United States of America 20190222 11

Major histocompatibility complex (MHC) genes encode proteins that initiate adaptive immune responses through the presentation of foreign antigens to T cells. The high polymorphism found at these genes, thought to be promoted and maintained by pathogen-mediated selection, contrasts with the limited number of MHC loci found in most vertebrates. Although expressing many diverse MHC genes should broaden the range of detectable pathogens, it has been hypothesized to also cause deletion of larger frac ...[more]

PMID: 30796191

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Project description:Bovine leukocyte antigens (BoLA) are extensively used as markers for bovine disease and immunological traits. However, none of the BoLA genes in Southeast Asian breeds have been characterized by polymerase chain reaction (PCR)-sequence-based typing (SBT). Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey, Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were also examined. BoLA-DRB3 PCR-SBT identified 78 previously reported alleles and five novel alleles. The number of BoLA-DRB3 alleles identified in each breed from the Philippines was higher (71 in Philippine native cattle, 58 in Brahman, 46 in Holstein × Sahiwal, and 57 in Philippine native × Brahman) than that identified in breeds from other countries (e.g., 23 alleles in Japanese Black and 35 in Bolivian Yacumeño cattle). A phylogenetic tree based on the DA distance calculated from the BoLA-DRB3 allele frequency showed that Philippine native cattle from different Philippine islands are closely related, and all of them are closely similar to Philippine Brahman cattle but not to native Japanese and Latin American breeds. Furthermore, the BoLA-DRB3 allele frequency in Philippine native cattle from Luzon Island, located in the Northern Philippines was different from that in cattle from Iloilo, Bohol, and Leyte Islands, which are located in the Southern Philippines. Therefore, we conclude that Philippine native cattle can be divided into two populations, North and South areas. Moreover, a neutrality test revealed that Philippine native cattle from Leyte showed significantly greater genetic diversity, which may be maintained by balancing selection. This study shows that Asian breeds have high levels of BoLA-DRB3 polymorphism. This finding, especially the identification of five novel BoLA-DRB3 alleles, will be helpful for future SBT studies of BoLA-DRB3 alleles in East Asian cattle.

Dataset Information

Major histocompatibility complex class I diversity limits the repertoire of T cell receptors.

Publications

Major histocompatibility complex class I diversity limits the repertoire of T cell receptors.

Similar Datasets

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