DISTINCT REQUIREMENTS AMONG MEMBERS OF THE LY49 RECEPTOR FAMILY IN ADAPTIVE NK CELL RESPONSES

Abstract

Immunological memory is a hallmark of the adaptive immune system. However, mounting evidence over the last decade has revealed that Natural Killer (NK) cells, a subset of innate lymphoid cells, can also mediate antigen-specific memory responses. Even though the existence of NK cell memory has been established, the mechanisms behind the adaptive NK cell responses, particularly the receptors involved in antigen recognition, remain poorly understood. This thesis investigates the role of Ly49 receptors, a family of class I MHC receptors in mice, in adaptive NK cell responses and shows that the requirement for Ly49 receptors in generating NK cell memory is not uniform. Specifically, it was found that inhibitory receptors Ly49C and/or Ly49I are indispensable for adaptive NK cell responses against haptens and peptides, irrespective of the MHC-I haplotype, whereas Ly49G is dispensable. Using soluble protein/MHC-I dextramers, this study further discovered that antigen-specific memory NK cells are long-lived and concentrated in Ly49C/I+ NK cell subsets in the liver. These findings point to a distinct role for Ly49C and/or Ly49I in adaptive NK cell responses and provide novel insight into the molecular and cellular mechanisms underlying the adaptive NK cell responses.