Thread by @jadav_md

My attempt on "Decoding the HLA" with tweetorial & some slides/VisualArts @kidney_boy @NSMCInternship @Nephro_Sparks @hswapnil @rheault_m @RenalFellowNtwk @ssfarouk #Transplant
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💥MHC complex
⚡️cluster of genes--> encodes HLA molecules
⚡️located on chromosome 6p21
⚡️over 200 genes; of which 40% involved in immune response
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💥HLA Genes:
⚡️main function is immune regulation
⚡️major barrier to transplant
⚡️gene products are histocompatibility molecules
⚡️highly polymorphic
⚡️significant linkage disequilibrium 👇
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💥MHC-HLA genome-> divided into 3 regions
⚡️Class I: molecules present on nucleated cells
⚡️Class II: present on antigen presenting cells
⚡️Class III: are NOT histocompatibility genes
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💥HLA Class I
⚡️Classical: HLA-A, -B, -C antigens
⚡️Non-classical: HLA -E, -F, -G antigens
⚡️Class I like antigens: MICA, MICB 👇
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💥HLA Class II
⚡️encodes HLA -DP, -DQ, -DR molecules
⚡️expressed on antigen presenting cells
⚡️presents antigens to CD8 T cells 👇
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💥HLA Class III
⚡️not involved in histocompatibility
⚡️encodes complement proteins like C2, C4, cytokines
⚡️has both immune and non-immune genes 👇
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💥HLA - Structure
⚡️Class I has heavy glycoprotein alpha chain bound to beta 2 microglobulin (gene on chromosome 15). Alpha chain has three domains and is transmembrane
⚡️Class II has both alpha & beta chains
⚡️peptide groove is highly polymorphic region 👇
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💥HLA Class I Antigen Processing & Presentation
⚡️Altered self or/viral protein --> degraded intracellularly into peptides by proteases --> which fit into peptide groove--> transferred to cell surface to present to CD8 T cells 👇
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💥HLA Class II Antigen Processing & Presentation:
⚡️Exogenous antigen---> endocytosis--> degraded into lysosomes--> combines with MHC compartment-->attached to peptide groove--> transferred to cell surface--> present to CD4 T cells👇
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💥HLA typing:
⚡️to assess the HLA genotype
⚡️historically, it was done with serological microcytotoxicity using viable lymphocytes & panel of anti-sera
⚡️Now, done with DNA-based HLA typing which is more reliable, precise & offers stable nomenclature👇
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💥HLA nomenclature
⚡️serological typing defines " antigens"
⚡️DNA typing defines "alleles"
⚡️WHO nomenclature includes distinct fields seperated by colon ( : )for antigen, allele, specific protein, nucleotide substitution in coding & non-coding region👇
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💥HLA Haplotype and Inheritance:
⚡️HLA alleles from each parent is called haplotype
⚡️it is inherited in Mandelian fashion
⚡️co-domminantly expressed👇
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💥HLA antibody
⚡️preformed antibodies against HLA antigens are major transplant barriers and has significant impact on allograft survival
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💥Strategies to detect HLA Abs
⚡️PRA: % panel reactive antibodies to assess sensitization in general
⚡️Identification of specific antibodies in recipient
⚡️crossmatch when kidney is available👇
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💥Crossmatch -->three methods
⚡️standard complement dependent cytotoxicity CDC (1960s)
⚡️Flow T & B cells crossmatch (1980s)
⚡️Solid phase technologies using single or multiple alleles-👇
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💥Virtual Crossmatch
⚡️predicts presence of donor specific antibodies using solid phase without an actual crossmatch
⚡️compares recipient's HLA ab to donor HLA type to predict Xmatch results
⚡️its use in lieu of 'wet' crossmatch is on the rise👇
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💥Summary
⚡️methods for high resolution HLA typing & precise quantitation of HLA ab in transplant on the rise
⚡️impetus for virtual Xmatch
⚡️need for better understanding of immunogenicity of HLA molecules & the role of ab on graft survival.
Thank you 👇