Characterization of a polymorphism of CD4 in miniature swine.
A polymorphism of CD4 in miniature swine has been identified by failure of cells from some animals to react with mAb 74-12-4. The phenotypic, molecular genetic, and functional characteristics of these animals have been defined. Cells from heterozygous animals bear approximately 50% the number of 74-12-4-reactive molecules on their surface as do cells from animals homozygous for the wild type. Animals of both phenotypes demonstrate similar flow cytometric profiles for CD8+ T cells. Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4. CD4 allelism is confirmed by Southern blot analysis, revealing RFLP. Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes. Proliferative responses to PHA and alloantigen stimulation by a full haplotype mismatch or a class II mismatch alone are equivalent for animals of both phenotypes. These data suggest that the allelic form of CD4, designated CD4.2 in contrast to the wild-type CD4.1, is capable of performing normally as an accessory molecule in the generation of immune responses. Furthermore, antixenogeneic responses to C57B10.BR were equivalent, suggesting that both CD4 molecular types may be capable of interacting with xenogeneic class II molecules. Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules.
Sundt
T M
TM
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
LeGuern
C
C
Germana
S
S
Smith
C V
CV
Nakajima
K
K
Lunney
J K
JK
Sachs
D H
DH
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011110:Polymorphism, Genetic; D013552:Swine; D013556:Swine, Miniature / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens