Science - USA (2020-06-05)

priming was necessary to generate memory
(fig. S1B). Polymorphism in the non-MHC
signal regulatory protein alpha (Sirpa) gene,
which is known to trigger the primary mono-
cyte alloresponse ( 8 ), was required (fig. S1C).

A database search across 17 mouse genomes

for potential MHC-I–binding molecules on

myeloid cells identified several families of

polymorphic immunoglobulin (Ig) superfam-

ily receptors. Among these were the paired

Ig-like receptors (PIRs), which are orthologs of

human leukocyte Ig-like receptors (LILRs) ( 10 ).

Closely linked genes coding for six PIR-A pro-

teins and one PIR-B protein are located on mouse

chromosome 7 ( 11 ). PIR-B is nonpolymorphic

Daiet al.,Science 368 , 1122–1127 (2020) 5 June 2020 2of6

Fig. 1. Monocyte and

macrophage memory

specific to allogeneic

MHC molecules.(Ato

D) Monocyte responses in

immunized mice measured

as monocyte-derived den-

dritic cells (Mo-DCs)

in the graft (n=5to

12 mice;N=1to2exper-

iments). d, day. (E) Mono-

cytes from immunized mice

transfer memory to naïve

recipients (n=2to4;

N=1to3).syn,syngeneic;

allo, allogeneic. (F)Allo-

specific killing of carboxy-

fluorescein diacetate

succinimidyl ester (CFSE)–

labeled cells in immunized

mice (n=6;N=2).(Gand

H) Nonself MHC recogni-

tion is necessary for elicit-

ing monocyte (n=6;N=1)

(G) and macrophage

(n=6;N= 2) (H) memory.

Killing of target cells

lacking nonself MHC

(BALB.B) or MHC-I (B2m–/–)

is significantly diminished

(H). Assays were performed

7 days after immunizing

B6-Rag−/−Il2rg−/−mice.

(I) Allogeneic MHC-I tet-

ramer (tet) binding to

macrophages from

BALB/c-immunized

B6-Rag−/−Il2rg−/−hosts

(representative of

three experiments). Max,

maximum. Statistical

analyses: mean and

individual biological

replicates [(A) to (H)];

one-way analysis of vari-

ance (ANOVA) [(A) to

(C), (F), and (H)]; or two-

tailed Student’sttest

[(D),(E),and(G)].*P<

0.05; **P< 0.01; ***P<

0.001; ****P< 0.0001;

ns, not significant.

RESEARCH | REPORT