BoLA class II polymorphism and immune response to Mycobacterium bovis antigens in vitro

Abstract

Summary In a sample of 47 Holstein‐Friesian calves, experimentally sensitized in vivo with a suspension of killed Mycobacterium bovis the BoLA class‐II polymorphism was analysed at the DQA, DQB, and DRB loci to define its role in the specific immune response. Lymphocyte proliferation under PPD stimulation, phagocytosis of killed M. bovis cells, and the humoral response to PPD antigens, tested by ELISA, were performed in vitro 21 days after sensitization to evaluate the specific immune response. All the animals responded well to the immune test. The humoral response was only slightly affected by some alleles in the D subregions investigated. Lymphocyte proliferation was significantly, and positively, affected by DQA*5, DQB*5, and DRB*5B+5C of the linkage group DH*18A. In particular, the effect of DRB*5C alone was more than two times higher than the standard deviation. Phagocytosis was significantly and negatively affected by DQA*9B and DQB*9B of the linkage group DH*22B, and also by DQA*1A, DQB*1, and DRB*1A of the linkage group DH*24A. In these specific experimental conditions, the results demonstrate that the humoral response is only slightly under the control of some class‐II alleles, while lymphocyte proliferation and phagocytosis are affected. The DRB locus shows a major effect on lymphocyte proliferation. Résumé Le polymorphisme de BoLA classe II a été analysée au DQA, DQB et DRB loci pour definir son rôle dans la réponse immune specifique relative à un groupe de 47 veaux Holstein Friesian sensibilisés d'une façon expérimentale in vivo avec une suspension de M. bovis mort. La proliferation de Lymphocites sous PPD stimulation aussi bien que la phagocitosis de cellules mortes de M. bovis et la réponse humoral aux antigens PPD avec le test ELISA a été faite in vitro 21 jours après la sensibilisation pour evaluer la réponse immune specifique. Tous les animaux ont bien répondu à tous les tests d'immunité. La réponse humoral a été influencée lèggérmente par aucun allèle des sous‐regions D investiguées. La proliferation des Lymphocites a été remarquablement et positivement influencée par les allèles DQA*5, DQB*5 et DRB*5B+5C du groupe de linkage DH*18A. En particuler l'effect du DRB*5C a été deux fois plus grand que l'écart‐type. La phagocitosis a été remarquablement et negativement influencée par DQA*9B et DQB*9B du groupe de linkage DH*22B aussi que par DQA*1A, DQB*1 et DRB*1A du groupe de linkage DH*24A. Les resultats demontrent que la réponse humoral est seulement en part sous le contrôl de quelque allèle de le classe II, d'autre part dans nos conditions experimentales specifiques la lymphoproliferation et la phagocitosys sont influencées. Le locus DRB démontre un effect important sur la lymphoproliferation liée à l'allèle DRB*5C. Resumen El polimorfismo de clase BoLA II fue analisado en loci DQA, DQB et DRB para definir su efecto en la inmmunidad specifica relativa a un grupo de 47 novillos Holstein Friesian sensitizadas experimentalmente en vivo con una suspension de M. bovis matado. La proliferacion de Lympo...

Co-infection with Mycobacterium bovis does not alter the response to bovine leukemia virus in BoLA DRB3*0902, genetically resistant cattle

“…The BoLA region has shown association with several diseases in cattle; in particular BoLA DRB alleles have been associated with variation in T-cell responses to M. bovis in Holstein calves (Casati et al, 1995). In our study, no association was observed between the BoLA genotype and reactor, suggesting that genetic selection for BLV resistant animals would not increase the herd susceptibility to TB.…”

Bovine tuberculosis: the genetic basis of host susceptibility

“…Other biologically plausible potential candidate genes, primarily from the immune system, the interface of hostpathogen interaction, have been suggested. The bovine MHC, or BoLA region, has shown association with several diseases in cattle (Lewin et al 1999) and, in particular, BoLA DRB alleles have been associated with variation in T-cell responses to M. bovis antigens studied in vivo in a population of 47 Holstein calves (Casati et al 1995). Similarly, the bovine orthologue of human DC-specific ICAM-3 grabbing non-integrin C-type lectin (DC-SIGN) gene has recently been identified and functionally characterized (Yamakawa et al 2008).…”

Genetic variation and responses to vaccines

“…DQ is more complicated: in about half of the haplotypes that have been tested there are duplicated DQA and DQB genes. It is clear that, in cattle, BoLA class II polymorphism plays a role in observed variability in immune responsiveness (Glass et al, 1991(Glass et al, , 2000Glass andMillar, 1994, 1995;Casati et al, 1995;van Lierop et al, 1995a;Newman et al, 1996;Garcia-Briones et al, 2000;Sitte et al, 2002). There are many alleles for DRB3 (104 alleles with 50 major types) and for DQA (47 alleles and 20 major types) and DQB (49 alleles and 30 major types) (http://www.projects.roslin.ac.uk/bola/) ( Fig.…”