Genetic and environmental determinants of human TCR repertoire diversity

T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on...

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Veröffentlicht in:Immunity & ageing Jg. 17; H. 1; S. 26 - 7
Hauptverfasser: Krishna, Chirag, Chowell, Diego, Gönen, Mithat, Elhanati, Yuval, Chan, Timothy A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 04.09.2020
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Adaptive immunity
Age
Aging
Analysis
Antibodies
Biomedical and Life Sciences
Biomedicine
Clinical Nutrition
Cytomegalovirus
Entropy
Genetic aspects
Geriatrics/Gerontology
Health aspects
Heterozygosity
Heterozygote advantage
Histocompatibility antigen HLA
HLA antigens
Hypotheses
Immune response
Immunogenetics
Immunology
Infection
Infections
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Peptides
Polymorphism
Public Health
Short Report
T cell receptor repertoire
T cell receptors
T cells
Infection
Aging
T cell receptor repertoire
Immunogenetics
Major histocompatibility complex
Heterozygote advantage
ISSN:1742-4933, 1742-4933
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Abstract T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
AbstractList T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity. Keywords: Major histocompatibility complex, Heterozygote advantage, T cell receptor repertoire, Infection, Aging, Immunogenetics
Abstract T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
ArticleNumber 26
Audience Academic
Author Chan, Timothy A.
Krishna, Chirag
Chowell, Diego
Elhanati, Yuval
Gönen, Mithat
Author_xml – sequence: 1
  givenname: Chirag
  surname: Krishna
  fullname: Krishna, Chirag
  organization: Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
– sequence: 2
  givenname: Diego
  surname: Chowell
  fullname: Chowell, Diego
  organization: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center
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  givenname: Mithat
  surname: Gönen
  fullname: Gönen, Mithat
  organization: Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research
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  givenname: Yuval
  surname: Elhanati
  fullname: Elhanati, Yuval
  email: elhanaty@mskcc.org
  organization: Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research, Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center
– sequence: 5
  givenname: Timothy A.
  surname: Chan
  fullname: Chan, Timothy A.
  email: chant@mskcc.org
  organization: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Weill Cornell School of Medicine, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32944053$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Infection
Aging
T cell receptor repertoire
Immunogenetics
Major histocompatibility complex
Heterozygote advantage
Language English
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Snippet T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors...
Abstract T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell...
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SubjectTerms Adaptive immunity
Age
Aging
Analysis
Antibodies
Biomedical and Life Sciences
Biomedicine
Clinical Nutrition
Cytomegalovirus
Entropy
Genetic aspects
Geriatrics/Gerontology
Health aspects
Heterozygosity
Heterozygote advantage
Histocompatibility antigen HLA
HLA antigens
Hypotheses
Immune response
Immunogenetics
Immunology
Infection
Infections
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Peptides
Polymorphism
Public Health
Short Report
T cell receptor repertoire
T cell receptors
T cells
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Title Genetic and environmental determinants of human TCR repertoire diversity
URI https://link.springer.com/article/10.1186/s12979-020-00195-9
https://www.ncbi.nlm.nih.gov/pubmed/32944053
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