Non-classical Major Histocompatibility Complex Class Makes a Crucial Contribution to Reproduction in the Dairy Cow

Abstract

Abstract. The aim of this study was to evaluate the effect of classical and non-classical major histocompatibility complex (MHC) on the reproduction in the dairy cow. Nine pairs of MHC-I genes were chosen according to their homology and possible function, and their transcription levels in maternal peripheral blood mononuclear cells (PBMCs) from all three trimesters and transcription levels in fetal tissues were compared to evaluate their contributions to cattle reproduction. The results showed that three non-classical genes were variably expressed in PBMCs of pregnant cows. MICB was downregulated in the first and second trimesters (P<0.05), but recovered back to the level in replacement heifers in the last trimester (P>0.05). BoLA-NC1* was upregulated in the first and last trimesters (P<0.001) but no different in the second trimester (P>0.05). BoLA-NC3* was upregulated in all trimesters (P<0.001). On the other hand, MICB was upregulated in fetal ear tissues (P<0.001), and BoLA-NC1* was almost silent in both fetal placenta and ear tissues (P<0.001); however, BoLA-NC3* was upregulated in both the fetal placenta and ear tissues (P<0.001). These results suggested that non-classical gene BoLA-NC1* increased maternal immunity against the fetus, which was inhibited by BoLA-NC3*. BoLA-NC3* also inhibited fetal autoimmunity. Apoptosis of the fetal placenta could reduce itself expressing MICB, and upregulated expression of MICB in ear tissues was favorable for the fetus to escape autoimmunity. On the other hand, downregulated expression of MICB in the fetal placenta allows for placental decoherence from the maternal placentome, which was beneficial to fetus delivery. Although classical genes were expressed differentially, their effects were restricted because of heavy chain deficiency. Key words: Diary cow, MHC-I, Reproduction (J. Reprod. Dev. 58: [569][570][571][572][573][574][575] 2012) M ajor histocompatibility complex (MHC) is a large gene family in most vertebrates, and makes crucial contribution to immune responses [1][2][3][4][5][6]. Similar to human MHC, MHC-I in the bovine is further categorized as classical molecules and non-classical molecules [7]. Classical class I genes are highly polymorphic and expressed in most somatic cells, and these class proteins present peptides from the animal own proteins or from intracellular pathogens to T cell receptors on CD8 + and cytotoxic suppressor T lymphocytes. Furthermore, classical class I proteins serve as the ligand for inhibitory receptors on natural killer (NK) cells and other leukocytes [7][8][9]. Non-classical class I genes are monomorphic or oligomorphic and have restricted cellular expression [8]. Although non-classical class I proteins have diverse functions, one important function is to act as ligands for inhibitory leukocyte receptors, including receptors encoded in the natural killer cell group 2D (NKG2D) complex and the leukocyte receptor complex [10][11][12].A fetus containing parental MHC-I genes is a semi-allograft to the dam. So the immunotolerance of...

Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

“…Increased transcription of NC3 at all stages of gestation in the intercotyledonary tissues is in agreement to a previous report (Shu et al, 2012) that studied the last trimester of gestation, and suggests that NC3 may act as an inhibitor of the maternal immune response Columns represent geometric means and standard error (n = 5) of fold change in transcription in comparison with uninfected controls. There were no statistically significant differences (p > 0.05).…”

“…NC1 had low levels of transcription both in the placentome and intercotyledonary tissues throughout the gestation, which is similar to a previous report (Shu et al, 2012). Although the function of bovine NC1 is largely unknown, it is thought that NC1, with its large number of splicing variants (Birch et al, 2008b), generates proteins that are anchored in the membrane or soluble, which may modulate immune tolerance in cattle (Davies et al, 2006).…”

“…Apparently these differences between species do not negatively affect the outcome of gestation (Joosten et al, 1991), and it may actually reflect evolutionally adaptations that may have been influenced by the strikingly morphological and physiological differences among the placenta in different species. In spite of previous studies demonstrating expression of MHC-I in bovine trophoblasts and maternal blood cells at the last trimester of gestation (Davies et al, 2006;Shu et al, 2012), expression of non-classical MHC-I by trophoblasts from different regions of the placenta and different stages of gestation remains unknown.…”

“…qPCR parameters were: 50 • C for 2 min, 95 • C for 10 min, 40 cycles of 95 • C for15 s and 60 • C for 1 min, using a StepOnePlus Real-time PCR System (Applied Biosystems, USA). qPCR was performed using a generic MHC class I primer pair named Bov 7 and 11 (Birch et al, 2006), which amplifies sequences of classical MHC class I, and sequences of the non-classical MHC class I locus NC1; and primer pairs for amplification of sequences of the non-classical MHC class I loci: NC1, NC3, and MIC-B (Shu et al, 2012), which are described in Table 1. C t values were normalized based on GAPDH transcription, and analyzed by the comparative C t method (2 − C t ) described by Livak and Schmittgen (2001).…”

Major Histocompatibility Complex-Associated Resistance to Infectious Diseases: The Case of Bovine Leukemia Virus Infection

“…To date, 96 BoLA-A alleles are listed on the Immuno Polymorphism Database (IPD)-MHC database [26], and 29 different haplotypes have been identified, expressing between one and three combinations of these classical class I genes [27,28]. The nonclassical BoLA class I genes include NC1, NC2, and NC3, encoding molecules with a relevant role during reproduction in dairy cows [29].…”