Nomenclature

Question 1

Epitope

Answer 1

• The three-dimensinoal structure which is the binding site for antibody.
• An antigen may have multiple eipitopes

Question 2

Epitope Group

Answer 2

• A family of antigens which shares one or more epitopes that result in repeatble patterns of antibody0binding reactivity
• Some epitopes are broadly shared between antigens and between loci
• Some epitopes are very restricted and may define single antigen specificities

Question 3

Epitope mapping

Answer 3

• Analysis of the pattern of antibody binding across multiple groups of HLAs and/or analysis of shared amino acid sequences between HLAs
• Used to predict likelihood of antibody reactity and rejection of transplanted organs and tissues

Question 4

Split

Answer 4

• Antigen specificity that may be recognized from part of a broader pattern of reactitivy.
• For example, HLA-B17 was split into HLA-b57 and HLA-B58
• The “ultimate” split is an allele.

Question 5

Allele

Answer 5

• Alternate nucleotide sequence at a gene
• can differ by a single nucleotide
• May or may not change the amino acid coded by the nucleotide triplet (codon) due to the degeneracy (redundancy) of the genetic code
• “silent” changes to not change sequence and require sensitive molecular techniques for detection
• nucleotide changes that are present in more than 15 of population are considered to be a polymorphism (allele)
• Most genes have a very common or “wild type” allele and rare allelic polymorphisms or mutations.
• There is no “wild type” for MHC due to massive polymorphism

Question 6

Antigen versus allelic complexity of HLA loci

Answer 6

locus - antigens - alleles
A - 28 - > 5900
B - 62- > 7100
C - 10 - > 5700
DR - 24 - > 3300
DQ - 9 - > 1700
DOP - 6 - > 1500

Question 7

Fourth HLA Workshop

Answer 7

• “W” placed in front of the next number in the sequence for the name of the antigen
• When a “new” HLA was accepted, the workshop designation was removed
• Worked for A and B, but did not carry over to C where numbering stared over at 1 for each new locus
• “W” was changed to “w”
• HLA-C has added naming complextity of retaining the use of the “w” before the antigen name (HLA-Cw7) to distinguish from the names of the complement proteins. Cw is used for HLA-C antigens 1 through 10

Question 8

Bw4 and Bw6

Answer 8

• Two specificities that were identified very early
• found to be present with many HLAs and were called “broad” antigens
• Subsequently, they were identified as epitopes found on multiple HLA Class I antigens, and can be used to assist in differentiating related antigens
• So far, no antigen has been identified that has both the Bw4 and Bw6 epitopes

Question 9

Public and Private epitopes

Answer 9

• Public epitiopes are present on multiple antigens
• Private epitopes are distinct and are considered as specific or identifying for indiviudual HLA
• some public epitopes can exists between HLA loci. for example sharing of the Bw4 epitope across many HLA-B antigens and some member of three broad HLA-A antigen groups

Question 10

HLA naming convention

Answer 10

HLA-A*31:01:02:03 [HLA-A31(19)]

• gene locus followed by * denotes allelic status of name
• allelic family name is next (30)
• alleles in family delimited by colon
• second colon is added when there are allelic variants that do not change the amino acid sequence “silent varients”
• digits beyond the third colon (fourth group) indicate alleles in which the variabtion occurs in an intro or the untranlsted sequences flanking the exons
• original intention was for the allele family name (HLA-A*02) to correspod to the antigenic specificity but it may not. Two reasons:
• first, most are identtified now my mollecular methods and no serological studies have benn performed
• Second, many HLA alleles are recombinations between alleles at a gene locus or recombinations between loci that result in novel combinations of serological “specificities”
• As a result, the WHO wrote in 2008: “the allele name should be seen as no more than a unique designtation”

Question 11

Abnormally (or alternatively) expressed HLA alleles

Answer 11

designated by a capital letter following the allele name
(eg: HLA-A2*:02:101:01:02N)
N= null
L = low expressions
S = secreted but not expresed on the cell surface
Q = questional expression

Question 12

Ambiguous HLA allele typings

Answer 12

• P grouping (e.g. HLA-A*01:01P) are used to simplify reporting of HLA alleles that have the same antigen-binding domains
• P designation follows the 2 field allele designation of the lowest numbered allele in the grouop, and will contain a minimum of four digits.
• G grouping (A*01:01:01G) simplify reporting of ambiguous typings for HLA alleles that share nucleotide sequences across the oliogopeptide binding domains (exons 2 and 3 for class 1 and exon 2 for class II)
• G group designations follow the first three fiels of the allele designation for the lowest numbered allele in the group and must have at least six digits
• There are gals in the ordinal series! either through misidentificatios based on incomplete sequences or errors.