MHC class I specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response

Makoto Yawata, Nobuyo Yawata, Monia Draghi, Fotini Partheniou, Ann Margaret Little, Peter Parham

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Variegated expression of 6 inhibitory HLA class I-specific receptors on primary NK cells was studied using high-dimension flow cytometry in 58 humans to understand the structure and function of NK-cell repertoires. Sixty-four subsets expressing all possible receptor combinations were present in each repertoire, and the frequency of receptor-null cells varied among the donors. Enhancement in missing-self response between NK subsets varied substantially where subset responses were defined by donor KIR/HLA allotypes, reflecting the differences in interaction between inhibitory receptors and their ligands. This contrasted to the enhancement conferred by NKG2A, which was constant and of intermediate strength. We infer a mechanism that modulates frequencies of the NK subsets displaying diverse levels of missing-self response, a system that reduces the presence of KIR-expressing subsets that display either too strong or too weak a response and effectively replaces them with NKG2A-expressing cells in the repertoire. Through this high-resolution analysis of inhibitory receptor expression, 5 types of NK-cell repertoire were defined by their content of NKG2A +/NKG2A - cells, frequency of receptor-null cells, and degree of KIR receptor coexpression. The analyses provide new perspective on how personalized human NK-cell repertoires are structured.

Original languageEnglish
Pages (from-to)2369-2380
Number of pages12
JournalBlood
Volume112
Issue number6
DOIs
Publication statusPublished - Sep 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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