Role of MHC in Disease Resistance PDF

Summary

This presentation discusses the role of the Major Histocompatibility Complex (MHC) in disease resistance. It covers MHC class I and class II proteins, their functions in antigen presentation, and involvement in various species such as bovine, buffalo, and ovine. The presentation also examines MHC genomic organization and disease association.

Full Transcript

ROLE OF MHC IN DISEASE RESISTANCE PRESENTED BY- Dr Shraddha Dwivedi MAJOR HISTOCOPATABILITY COMPLEX MHC is a cluster of genes some of which codes for proteins expressed On the surface of the cytoplasmic membrane of somatic cells. These proteins serve as unique self markers which participate...

ROLE OF MHC IN DISEASE RESISTANCE PRESENTED BY- Dr Shraddha Dwivedi MAJOR HISTOCOPATABILITY COMPLEX MHC is a cluster of genes some of which codes for proteins expressed On the surface of the cytoplasmic membrane of somatic cells. These proteins serve as unique self markers which participate in cell-to-cell recognition and communication. The principal function of MHC is to present antigen to T- Cell to discriminate between self and non self cells NOMENCLATURE FOR MHC IN THE MAJOR VARIOUS SPECIES HISTOCOMPATIBILI Species Nomenclature Full Form TY COMPLEX Mouse H-2 Histocompatability-2 (MHC) Rat RT1 Rat Locus 1 Guinea Pig Lymphocyte Guinea Pig GPLA Antigens Human HLA Human Lymphocyte MHC is located on the Antigens Bovine Lymphocyte short arm of chromosome Cattle BoLA Antigens 6 in humans, chromosome Buffalo Lymphocyte Buffalo BuLA Antigens 17 in mice, chromosome Sheep OLA Ovine Lymphocyte Antigens 23 in cattle, chromosome Goat GLA Goat Lymphocyte 7 in pigs, chromosome 2 in Antigens buffalo, chromosome 23 in Swine Lymphocyte Swine SLA Antigens goat and chromosome 20 Domestic Fowl B-Complex Blood Group B-Complex in sheep Dog Lymphocyte Dog DLA Antigens Feature MHC Class I MHC Class II Primarily on antigen- Found on all nucleated presenting cells (APCs) like Expression cells dendritic cells, macrophages, and B cells Presents endogenous Presents exogenous Antigen Type (intracellular) antigens (extracellular) antigens Interacts with CD8+ cytotoxic T cells CD4+ helper T cells Binds shorter peptides (8- Binds longer peptides (12- Peptide Binding Groove 10 amino acids) 25 amino acids) Cell-mediated immunity Helper-mediated immunity Immune Response Type (targeting infected or (coordinating broader abnormal cells) immune response) CD4 binds to the b2 region Binding Site CD8 binds to the a3 region Bovine MHC Location: Bta 23 band 22 Unique feature: Inversion bifurcates class II Class I - 20 seq express :9 expressed at lower rate :6 pseudogenes Class II - DRA, DRB3, DQA, DQB1, DQB2 Some inter-locus recombination results in production of “hybrid genes” Genomic organization of BoLa (Bovine MHC) Cattle MHC and Disease association Cattle MHC and Disease association Cont…… BUFFALO MHC The buffalo lymphocyte antigen system termed as BuLA. The MHC gene was localized to Chromosome 2 (BBU2) in BUFFALO river buffalo. There is a close linkage between class I and class II regions in buffaloes. MHC Evolutionary analysis revealed numerous trans-species polymorphism from water buffalo assigned to at least 3 different loci (Bubu-DQA1, DQA2, DQA3). Alleles of both the sub-species intermixed within the cluster, showing convergent evolution of MHC alleles in bovines. Mishra et al (2016) found distribution of the buffalo DQA sequences in two major clusters of DQA1 and DQA2 genes, sharing common lineages with corresponding cattle alleles, possibly due to trans-species evolution. Extensive duplication of DQA locus found in swamp buffaloes sharing DQA1, DQA2, and DQA3 alleles in different combinations in duplicated haplotypes Ovine MHC Found in Chromosome no-20 Ovar-DRA: Expressed, Low polymorphism (2 alleles) Ovar-DRB 1: Expressed. Functionally equivalent to BoLA-DRB3. Highly polymorphic, with 74 alleles 0var-DRB2: Psedogene (lacksthe exon 1 and exon 2, and has two premature stop codons and other mutations that render it non-functional) DQA and DQB: Some individuals carry a single copy of DQA and DQB genes ,whereas others have duplicated haplotypes. The ovine DQ region encompasses 130 kb, with the DQ1 and DQ2 sub- regions located 22 kb apart and both Ovar-DQA Ovine MHC THANK YOU

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