HLA System

Question 1

Bennett-Goodspeed antigens

Answer 1

Bg(a) - B7
Bg(b) - B17 (B57/B58)
Bg(c) - A28 (A68/A69)

Question 2

When is HLA present in a soluble form?

Answer 2

At baseline, but it is increased in inflamed states (organ rejection, HIV infection).

Question 3

Compare the structures of MHC-I and MHC-II.

Answer 3

MHC-I is composed of an alpha 1/2/3 chain and beta-2 microglobulin. The protein binding cleft is in the alpha chain.

MHC-II is composed of heterodimers of alpha 1/2 and beta 1/2.

Question 4

HLA nomenclature: “w”

Answer 4

Formerly “workshop”, now used for…

1. Cw (to distinguish from complement)
2. Bw (public antigens)
3. Dw?

Question 5

What is the minimum exon sequencing required to define an HLA allele?

Answer 5

Must sequence exons 3 (MHC-II) or 2 and 3 (MHC-I).

Question 6

HLA nomenclature: N, L, S, Q, A, C

Answer 6

N: Null
L: Low expression
S: Secreted
Q: Questionable expression
A: Unknown
C: Cytoplasmic

Question 7

Break down HLA nomenclature: HLA-DRB1: AA : BB : CC : DD : E

Answer 7

AA: Serologic equivalent
BB: Allele
CC: Silent mutation
DD: Non-exonic mutation
E: Modifier

Question 8

How are antigens presented on MHC-I?

Answer 8

Cytoplasmic antigens are digested by LMP, and are transported to the cell surface by TAP.

Question 9

How are antigens presented on MHC-II?

Answer 9

An invariant chain “Ii” is replaced by an endocytosed antigen, then the entire molecule is translocatd to the surface.

Question 10

What are the MHC-I and MHC-II genes of significance?

Answer 10

MHC-I: HLA-A, HLA-B, HLA-C

MHC-II: DRA1, DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1)

Question 11

What is in MHC Class III?

Answer 11

Non-MHC genes that may or may not be related to immune signaling: Complement genes, 21-OH, and TNF.

Question 12

What are the “Ib” (“non-classical”) genes in the MHC-I region?

Answer 12

HLA-E (plays a role in NK cel surveillance)
HLA-G (expressed in trophoblast)
HLA-H (misnomer for HH/HFE gene)

Question 13

What are the chances of finding an MHC-matched sibling given a number of siblings “n”?

Answer 13

1 - (3/4)^n

Question 14

What DNA assays can be used to assess an HLA allele?

Answer 14

Sequence specific oligonucleotides (forward or reverse)
Sequence specific primers
Sequencing: Sanger or NGS

Question 15

How do serologic HLA tests work?

Answer 15

Solid phase assays using patient plasma against either single antigen recombinant or T-cell derived beads.

Question 16

What transfusion concepts are affected by the HLA system?

Answer 16

Platelet refractoriness
TRALI
FNHTR
TA-GVHD

Question 17

What HLA alleles are associated with the following conditions: Celiac disease, ankylosing spondylitis, narcolepsy

Answer 17

Celiac: HLA-DQ2
AnkSpon: HLA-B27
Narcolepsy: HLA-DQ6