PMID- 32944053
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240429
IS  - 1742-4933 (Print)
IS  - 1742-4933 (Electronic)
IS  - 1742-4933 (Linking)
VI  - 17
DP  - 2020
TI  - Genetic and environmental determinants of human TCR repertoire diversity.
PG  - 26
LID - 10.1186/s12979-020-00195-9 [doi]
LID - 26
AB  - 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.
CI  - (c) The Author(s) 2020.
FAU - Krishna, Chirag
AU  - Krishna C
AD  - Computational and Systems Biology Program, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
FAU - Chowell, Diego
AU  - Chowell D
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
FAU - Gonen, Mithat
AU  - Gonen M
AD  - Department of Epidemiology and Biostatistics, Sloan Kettering Institute for 
      Cancer Research, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 
      2171 9952
FAU - Elhanati, Yuval
AU  - Elhanati Y
AD  - Department of Epidemiology and Biostatistics, Sloan Kettering Institute for 
      Cancer Research, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 
      2171 9952
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
FAU - Chan, Timothy A
AU  - Chan TA
AD  - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 
      New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
AD  - Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer 
      Center, New York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
AD  - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New 
      York, NY 10065 USA. GRID: grid.51462.34. ISNI: 0000 0001 2171 9952
AD  - Weill Cornell School of Medicine, New York, NY 10065 USA. GRID: grid.137628.9. 
      ISNI: 0000 0004 1936 8753
AD  - Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, 
      Cleveland, OH 44195 USA. GRID: grid.239578.2. ISNI: 0000 0001 0675 4725
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA205426/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20200904
PL  - England
TA  - Immun Ageing
JT  - Immunity & ageing : I & A
JID - 101235427
PMC - PMC7487954
OTO - NOTNLM
OT  - Aging
OT  - Heterozygote advantage
OT  - Immunogenetics
OT  - Infection
OT  - Major histocompatibility complex
OT  - T cell receptor repertoire
COIS- Competing interestsNot applicable.
EDAT- 2020/09/19 06:00
MHDA- 2020/09/19 06:01
PMCR- 2020/09/04
CRDT- 2020/09/18 05:49
PHST- 2020/05/14 00:00 [received]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/09/18 05:49 [entrez]
PHST- 2020/09/19 06:00 [pubmed]
PHST- 2020/09/19 06:01 [medline]
PHST- 2020/09/04 00:00 [pmc-release]
AID - 195 [pii]
AID - 10.1186/s12979-020-00195-9 [doi]
PST - epublish
SO  - Immun Ageing. 2020 Sep 4;17:26. doi: 10.1186/s12979-020-00195-9. eCollection 
      2020.