Table 1. Interactions underlying HLA class I disease associations in HTLV-1 infection.

Four HLA class I alleles are associated with disease (HAM/TSP) in HTLV-1 infection (model 1, index only). For each HLA allele we sought to determine the underlying mechanism by performing 5 multivariate logistic regressions (model 2–6), one for each of the distance metrics. The coefficient (Coeff) and P value for the index allele and the nearby alleles (similarity metric) are recorded below. For each of the index HLA alleles considered TCR.FS was associated with disease and in the same direction as the index allele; that is when the index was protective alleles with similar TCR binding (high TCR.FS) were protective and when the index was detrimental TCR.FS was detrimental (see row ‘TCR.FS’ in model 2, shaded). Furthermore, inclusion of TCR.FS in the multivariate analysis actually strengthened the effect of the index allele in every case (compare the magnitude of the coefficient for index in model 1 and index in model 2) indicating that removal of near alleles from the baseline made the ‘background’ alleles more dissimilar to the index. None of the other metrics were significant for any of the index alleles considered. Coeff <0 indicates reduced risk of HAM/TSP (i.e. a protective effect, ‘P’), Coeff >0 indicates increased risk of HAM/TSP (i.e. a detrimental effect, ‘D’). The odds ratio = exp(Coeff). The additional covariates age and gender were included in the regressions. Significance codes: p<0.001 ***; p<0.01 **; p<0.05 *; p<0.1. ; P values are two tailed.

			Index allele
Model	Covariate		A*02:06	A*02:07	C*08:01	B*54:01
1. Index only	Index	Coeff	−0.55 P	−1.27 P	−0.52 P	0.96 D
		P val	0.086 ·	0.0079 **	0.19	0.0056 **
2. Index + TCR.FS	Index	Coeff	−0.67	−1.32	−0.70	1.15
		P val	0.042 *	0.0057 **	0.086 ·	0.0014 **
	TCR.FS	Coeff	−5.48 P	−2.40 P	−1.66 P	1.57 D
		P val	0.00014 ***	0.017 *	0.075 ·	0.02 *
3. Index + iKIR.FS	Index	Coeff	−0.55	−1.26	−0.72	+0.82
		P val	0.08 ·	0.009 **	0.083 ·	0.02 *
	iKIR.FS	Coeff	−0.43 P	−0.36 P	−1.23 P	−0.87 P
		P val	0.51	0.63	0.12	0.11
4. Index + aKIR.FS	Index	Coeff	−0.55	−1.25	−0.51	+0.83
		P val	0.08 ·	0.009 **	0.20	0.019 *
	aKIR.FS	Coeff	−0.47 P	−0.41 P	0.18 D	−0.64 P
		P val	0.48	0.60	0.70	0.13
5. Index + LILRB1.S	Index	Coeff	−0.48	−1.36	−0.60	1.06
		P val	0.15	0.008 **	0.16	0.005 **
	LILRB1.S	Coeff	0.65 D	−0.47 P	−0.49 P	0.92 D
		P val	0.51	0.61	0.61	0.47
6. Index + LILRB2.S	Index	Coeff	−0.49	−1.13	−0.61	0.96
		P val	0.15	0.029	0.14	0.009 **
	LILRB2.S	Coeff	0.45 D	0.84 D	−0.73 P	−0.05 P
		P val	0.63	0.51	0.50	0.96