Naslov
Viral MHC Class I-like Molecule Allows Evasion of NK Cell Effector Responses In Vivo

Autori
Pyzik, M ; Dumaine, AA ; Charbonneau, B ; Fodil-Cornu, N ; Jonjić, S ; Vidal, SM.

Izvornik
Journal of immunology (0022-1767) 193 (2014), 12; 6061-6069

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
rodent ; natural killer cells ; viral infections ; MHC ; cell activation ; spleen and lymph nodes

Sažetak
The outcome of mouse CMV (MCMV) infection varies among different inbred mouse strains depending on NK cell effector functions governed through recognition receptor triggering. NK cells from different mouse strains possess diverse repertoires of activating or inhibitory Ly49 receptors, which share some of their polymorphic MHC class I (MHC-I) ligands. By examining the NK cell response to MCMV infection in novel BALB substrains congenic for different MHC (or H-2 in mice) haplotypes, we show that recognition of viral MHC-I-like protein m157 by inhibitory Ly49C receptor allows escape from NK cell control of viral replication. Dominant inhibition by Ly49C bound to self-H-2b encoded MHC-I molecules masks this effect, which only becomes apparent in distinct H-2 haplotypes, such as H-2f. The recognition of m157-expressing cells by Ly49C resulted in both decreased NK cell killing in vitro and reduced rejection in vivo. Further, control of infection with m157-deletant (Δm157) MCMV was improved in mice carrying H-2 molecules unrecognized by Ly49C but allowing expansion of NK cell effectors expressing activating Ly49L receptors. Hence, our study is the first, to our knowledge, to demonstrate that MHC-I mimicry strategies used by MCMV to avoid NK cell control are biologically relevant during in vivo viral infection. Of value for human studies is that only a few genetic assortments conditional on the repertoires of viral MHC-I-like proteins/host NK receptors/MHC haplotypes should allow efficient protection against CMV infection.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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