Thread by @ssfarouk

1/ A short #tweetorial introducing human leukocyte antigen (HLA) and typing...an important and often confusing topic in #transplantation #kidneytransplant

#FOAMed @MedTweetorials

What is an "HLA"?

2/

HLAs = cell surface proteins encoded by highly polymorphic major histocompatibility complex (MHC) genes on Ch 6 🧬

In #transplantation, HLA proteins are #polymorphic antigens ➡️ alloreactive trigger for the immune response ➡️ can ultimately lead to organ #rejection ☠️

3/ The 2 primary classes of MHC molecules are 1⃣ and 2⃣.

Class 1⃣ MHC are found on the cell surface of ALL nucleated cells + platelets. Their role is to present intracelleular peptide fragments to CD8 #Tcells

4/
Class 2⃣ MHC are found on the surface of "pro" antigen presenting cells (APCs), e.g. dendritic cells, B cells, mononuclear phagocytes, some endothelial cells.

They present extracellular peptides that are phagocytosed, digested in lysosomes ➡️ loaded onto class 2⃣ molecule

5/ 3 major genes encoded by class 1⃣ & 2⃣ HLA = A/B/C & DR/DP/DQ, respectively

Back to "polymorphic" - what does it mean?

A gene = polymorphic if > 1⃣ allele occupies that gene's locus within a population. So, there are hundreds of alleles that can occupy HLA loci above. 👇🏽

6/ We have 2⃣ alleles at each HLA locus: 1⃣ from biological mother & 1⃣ from biological father. This is co-dominant inheritance, both alleles are fully expressed.

Loci are inherited in a haplotype = combo of alleles at adjacent loci on a chromosome that are inherited together.

7/ HLA typing using 🧬 PCR techniques can be performed to identify one's HLA alleles. Allele level typing is > specific than serologic typing. 2 may share a SEROLOGIC type of 2 at the HLA-A locus - but both may have different A2 alleles.

Remember - HLA genes are POLYmorphic!

8/In summary,

1⃣ #HLA genes = highly polymorphic & encode cell surface proteins
2⃣Class I/II HLA present intra/extracellular peptides ➡️ CD8/CD4 #Tcells, respectively
3⃣The major Class I/II genes = A/B/C & DR/DP/DQ, respectively
4⃣Co-dominant inheritance

Next: Crossmatching!