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Citing this page: Lefranc, M.-P. and Lefranc, G. Human Gm, Km and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism In: B. Tait, F. Christiansen (Eds.), Immunogenetics, chap. 34, Humana Press, Springer, New York, USA. Methods Mol. Biol. 2012; 882, 635-680. PMID: 22665258

Km allotypes

Allotypes have been identified for the human IGKC gene and are designated as Km (for 'kappa marker') (previously Inv) [1-2].

Km allotype characterization

Km allotypes are determined by the hemagglutination technique inhibition [3-4]. There are three identified Km allotypes: Km1, Km2 and Km3. They correspond to IGKC amino acid changes at position 45.1 and 101, according to the IMGT unique numbering for C-DOMAIN (Table).

Km phenotypes and Km genotypes

Given the rarity of anti-Km2 and anti-Km3 reagent antibodies, only the Km1 allotype is tested in most of the population studies. In the table below are shown:

Km genotypes a Km phenotypes b
Sera tested for allotypes
Km1,Km2 and Km3		 Sera only tested for
allotypes Km1 and Km2		 Sera only tested for
allotype Km1
Km1/Km1 Km1 Km1,-2 Km1
Km1/Km3 Km1,3
Km1/Km1,2
or Km1,2/Km1,2		 Km1,2 Km1,2
Km1,2/Km3 Km1,2,3
Km3/Km3 Km3 Km-1,-2 Km-1

a Km alleles and genotypes were previously written underlined and using superscript (for example Km1/Km1).
b Numbers of the Km allotypes and phenotypes are written between parentheses.

Km phenotypes in Lebanese and Tunisian populations (LIGM data)

Km phenotypes Lebaneses [4] (1) Tunisians [5] Tunisian Berbers [6] (2)
Mahdia (2) Sfax (1) Kesra Takrouna-Jeradou Douiret-Chenini
Km1 Km1,-2 33 0 4 0 0 0
Km1,3 7 0 0 0
Km1,2 Km1,2 421 7 37 1 2 6
Km1,2,3 59 19 36 32
Km3 Km-1,-2 2584 163 101 60 85 69
Total number of individuals 3038 236 142 80 123 107

Km allele frequencies in Lebanese and Tunisian populations (LIGM data)

Km allele frequencies Lebanon [4] (1) Lebaneses [7] (1) Tunisians [5] (3) Tunisian Berbers [6] (2)
Sunnites Shiites Druzes Maronites Orthodox Greeks Catholic Greeks Armenians Mahdia (2) Sfax (1) Kesra Takrouna-Jeradou Douiret-Chenini
Km3 0.922 0.907 0.917 0.941 0.923 0.930 0.917 0.933 0.833 0.842 0.879 0.826 0.795
Km1,2 0.072 0.079 0.079 0.057 0.074 0.066 0.074 0.061 0.149 0.144 0.120 0.173 0.204
Km1 0.006 0.014 0.004 0.002 0.003 0.004 0.009 0.006 0.017 0.014 0.001 0.001 0.001
Total number of alleles 6076 552 644 472 1596 726 564 660 472 284 160 246 214

Km allele frequency overview

Km allele frequencies Caucasoids [9-18] Mongoloids and Negroids [12,16,19-21] Indians of South America [22-24]
Km3 0.9 0.8-0.5 0.4
Km1,2 0.08 0.2-0.5 0.5-0.6
Km1 0.01 0.01 0.01

Correspondence between Km alleles and IGKC allele names

Km alleles IGKC allele names Amino acid positions (4)
45.1 101
(46) (84)
153 191
Km3 IGKC*01
IGKC*02
IGKC*03
IGKC*05		 Ala
GCC		 Val
GTC
Km1,2 IGKC*04 Ala
GCC		 Leu
CTC
Km1 IGKC*06 (5) Val
(GTC)		 Leu
(CTC)

Description of mutations for the Km alleles

Description of mutations for the Km alleles is according to the IMGT unique numbering for C-DOMAIN. Between parentheses are shown the expected mutations responsible for the Km1 amino acid changes.

Km alleles Description of mutations
Km3 
 c134.1   ,A45.1  | g301   ,V101  |
Km1,2 
 c134.1   ,A45.1  | g301>c ,V101>L|
Km1 
(c134.1>t),A45.1>V|(g301>c),V101>L|

Km3, Km1,2 and Km1 allotypes on IGKC three-dimensional structure

Km allotypes
Fig. 1. Km3, Km1,2 and Km1 allotypes on the Homo sapiens IGKC three-dimensional structure

The C-KAPPA domain (encoded by IGKC*01) is from the b12 antibody (IMGT/3Dstructure-DB, code PDB:1hzh). The alanine Ala A45.1 (strand CD) and the valine Val V101 (strand F) are shown [32]. The A45.1 and V101 corresponds to the Km3 allotype. The A45.1 and L101 would correspond to Km1,2, and the V45.1 and L101 would correspond to Km1 [32].


Reference to be quoted for this figure [32]:
Lefranc, M.-P. and Lefranc, G. Human Gm, Km and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism In: B. Tait, F. Christiansen (Eds.), Immunogenetics, chap. 34, Humana Press, Springer, New York, USA. Methods Mol. Biol. 2012; 882, 635-680. PMID: 22665258 LIGM: 406


IMGT notes:
(1) Sera only tested for Km1 and Km2 allotypes. The Km1 and Km1,2 allele frequencies were calculated, and the Km3 allele frequency was deduced by difference.
(2) Sera tested for Km1, Km2 and Km3 allotypes.
(3) Another study on the same Tunisian populations provided similar frequencies [8].
(4) Amino acid positions according to the IMGT unique numbering for C-DOMAIN [30] (in bold), to the IMGT exon numbering (between parentheses) and to the Kabat numbering (in italics). Characterization of amino acids for Km allotypes are from [25-29].
(5) Not sequenced at the nucleotide level. Expected codons are shown between parentheses (G. Lefranc and M.-P. Lefranc, 13/05/2003) [31].
References:
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[3] Lefranc, G., Allotypes et haplotypes des immunoglobulines dans les communautés libanaises : intérêt exceptionnel en immunogénétique et séro-anthropologie.
Thèse de Doctorat d'Etat es Sciences Naturelles. Faculté des Sciences, Université de Rouen, 21 mars 1978.
[4] Lefranc, G. et al., Acta Anthropogenetica, 1, 34-45 (1976) LIGM:3. pdf
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[7] Lalouel, J.M. et al., Acta Anthropogenetica, 1, 15-33 (1976) LIGM:2.
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[25] Baglioni, C. et al., Science, 152, 1517-1519 (1966) PMID: 5934342.
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[27] Milstein C., Nature, 209, 370-372 (1966) PMID: 5920238.
[28] Milstein, C.P. et al., Nature, 248, 160-161 (1974) PMID: 4132042.
[29] Steinberg, A.G. et al., Immunogenetics, 2, 1-10 (1974).
[30] Lefranc, M.-P. et al., Dev. Comp. Immunol., 29, 185-203 (2005).
[31] Lefranc G. and Lefranc M.-P. The Immunoglobulin FactsBook, Academic press, London, UK, 458 pages (2001).
[32] Lefranc, M.-P. and Lefranc, G., Methods Mol. Biol. 882, 635-680 (2012). PMID: 22665258 LIGM: 406

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